gebhart/patrepeval huggingface dataset:
Novel Perovskite-Based Devices (2019)

Organic-inorganic hybrid perovskite attracts huge interests due to its outstanding properties. Here, three kinds of perovskite devices have been developed, including resistive switching memory, position-dependent photodetector and graphene-perovskite hybrid phototransistor. The resistive switching memory shows extremely low operating current and synaptic characteristics. The position-dependent photodetector could realize millimeter-scale detectivity. The phototransistor reaches the peak photoresponsivity of 600 A/W and shows great stability in ambient environment in 75 days. These results demonstrated that both 3D single crystals and 2D flakes of perovskites can be used for many fields, especially for electronic and opto- electronic device applications.
Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype (2010)

Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments.
Rapid, Efficient Synthesis of Heterobifunctional Biodegradable Dendrimers (2007)

A method for the preparation of heterobifunctional biodegradable dendrimers is described involving the preparation of a symmetric aliphatic ester dendrimer derived from 2,2-bis(hydroxymethyl)propanoic acid bearing a cyclic carbonate periphery, followed by opening of the carbonate moieties with a functional amine. This approach requiring no chromatographic purification steps was demonstrated with the preparation of a dendrimer bearing eight protected aldehydes and eight alkynes at its periphery.
A new technique for the characterization of long-range tertiary contacts in large RNA molecules: insertion of a photolabel at a selected position in 16S rRNA within the Escherichia coli ribosome (1997)

A new approach for inserting a photo-label at a selected position within the long ribosomal RNA molecules has been developed. The Escherichia coli 16S rRNA was cleaved at a single internucleotide bond, 1141-1142, with RNase H in the presence of a complementary chimeric oligonucleotide. 4-Thiouridine 5', 3'-diphosphate was ligated to the 3'-end of the 5'fragment at the cleavage site with T4 RNA ligase. The 16S rRNA fragments containing this added photo-reactive nucleotide were assembled together with total 30S ribosomal proteins into small ribosomal subunits. The ability of such 30S particles containing fragmented rRNA to form 70S ribosomes has been demonstrated previously. Crosslinks were induced within the 30S subunits by mild UV irradiation. The sites of crosslinking within the 16S rRNA were then analyzed using RNase H digestion and reverse transcription. Two crosslinks from the thio-nucleotide attached to nt C1141 of 16S rRNA were observed, namely to nt U1295 and G1272. These results are in agreement with the established proximity of helix 39 and 41 in the 3D structure of the 30S ribosomal subunit, as shown by other intra RNA crosslinking data. These data furthermore allow us to refine the structural arrangement of helices 41 and 39 relative to one another.
A Microprocessor Controlled Memory Tuning System (1979)

The introduction of the microprocessor has started a change in the field of electronics quite unlike that caused by the introduction of any other component. The tremendous control and decision making capabilities of the microprocessor have created applications which would not have been practical using previous technology. The single chip microcomputer has made application of microprocessor technology even more attractive for highly cost sensitive areas requiring a dedicated controller. Television tuning systems are just such an area. This paper describes the implementation of a microprocessor based memory tuning system. Discussed is the design of some of the hardware and software which best demonstrates the utilization of the characteristics of the microprocessor environment to produce a cost effective tuning system.
Rational Design of True Hirudin Mimetics:  Synthesis and Characterization of Multisite-Directed α-Thrombin Inhibitors (1996)

We describe here the design, synthesis, and activity of a novel class of alpha-thrombin inhibitors named hirunorms. They were rationally designed to interact through their N-terminal end with the alpha-thrombin active site in a nonsubstrate mode and to specifically bind the fibrinogen recognition exosite. An appropriate spacer that is able to properly orient the N-terminal end in the active site was also selected. This spacer allowed the size of the inhibitors to be reduced to about one-third of the amino acid residues in the hirudin sequence. Hirunorms specifically inhibit the amidolytic action of human alpha-thrombin toward a small chromogenic substrate. The most active compounds of the series, hirunorms IV and V, inhibit alpha-thrombin catalyzed hydrolysis of Tos-Gly-Pro-Arg-p-nitroanilide with K(i) = 0.09 and K(i) = 0.21 nM, respectively. Comparison of the anticoagulant properties of hirunorms, natural hirudin from the European leech Hirudo medicinalis, and the synthetic analog hirulog-1 revealed that hirunorm IV is about 10-fold and 3-fold more active, on a molar base, than hirudin and hirulog-1 in increasing the aPTT, PT, and TT of normal human plasma. The peculiar structure of hirunorms makes them stable to the amidolytic action of thrombin without the introduction of any peptide bond modification. These molecules display long-lasting activity in human plasma, due to the presence of several unnatural amino acids in susceptible positions. Hirunorms are potential candidates for injectable anticoagulants, due to their potency, specificity of action, long-lasting activity, and safety profiles.
Does the Antitumor Adenovirus ONYX-015/dl1520 Selectively Target Cells Defective in the p53 Pathway? (2001)

Increased knowledge of how normal cell growth is altered during tumorigenesis has led to the development of novel approaches to killing cancer cells. However, the application of novel tumor therapies, like conventional therapies, still depends on there being an effective means of selectively
Amelioration of Autoimmune Encephalomyelitis by Myelin Basic Protein Synthetic Peptide-Induced Anergy (1992)

Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the central nervous system that can be induced in susceptible strains of mice by immunization with myelin basic protein (MBP) or its immunodominant T cell determinants, serves as a model of human multiple sclerosis. Tolerance to MBP in adult mice was induced by intraperitoneal injection of synthetic peptides of immunodominant determinants of MBP and prevented MBP-induced EAE. Furthermore, tolerance-inducing regimens of peptides administered to mice after the disease had begun (10 days after induction with MBP) blocked the progression and decreased the severity of EAE. Peptide-induced tolerance resulted from the induction of anergy in proliferative, antigen-specific T cells.
Micropillar substrate influences the cellular attachment and laminin expression (2009)

Fibroblasts alter their mode of attachment and focal contact when placed on square arrays of silicon pillars. The pillars had 1-microm diameters with identical surface chemistry. Distance between pillars is 9 microm and height of pillars is 1, 5, or 10 microm on substrates. We found that these micropillars, rather than specific interactions, provided more opportunities for mechanical interlocking of the fibroblasts and acted as physical barriers that restrained cell migration. The cellular morphology and behavior is guidable by the height of pillars. In some cases, the fibroblasts filled in the intervals among several pillars; in others, a pillar protruded visibly through the cell body but did not pierce it, the cells were survived. Therefore, fibroblasts were immobilized upon in situ and the cytoplasma migrated outward to the bottom of the substrate subsequently. Laminin plays a critical role in cell attachment to the basement membrane. The results of laminin expression in fibroblasts suggest that pillar pattern appears to change cellular behavior and affect laminin expression significantly.
Molecular evolution and distribution of dengue viruses type 1 and 2 in nature (1990)

During the past several decades, dengue viruses have progressively extended their geographic distribution, and are currently some of the most important mosquito-borne viruses associated with human illness. Determining the genetic variability and transmission patterns of these RNA viruses is crucial in developing effective control strategies for the disease. Primer-extension sequencing of less than 3% of the dengue genome (across the E/NS1 gene junction) provided sufficient information for estimating genetic relationships among 40 dengue type 1 and 40 type 2 virus isolates from diverse geographic areas and hosts. A quantitative comparison of these 240-nucleotide-long sequences revealed previously unrecognized evolutionary relationships between disease outbreaks. Five distinct virus genotypic groups were detected for each of the two serotypes. The evolutionary rates of epidemic dengue viruses of types 1 and 2 were similar, although the transmission pathways of these viruses around the world are different. For dengue type 2, one genotypic group represents an isolated, forest virus cycle which seems to have evolved independently in West Africa. This is the first genetic evidence of the existence of a sylvatic cycle of dengue virus, which is clearly distinct from outbreak viruses.
A Wide-Band Phase-Feedback Inverse-Sine Phase Modulator with Application Toward a LINC Amplifier (1976)

A wide-band inverse-sine phase modulator is demonstrated. The modulator has application in a LINC amplifier for linear amplification at microwave frequencies using commonly available saturating amplifiers or injection-locked oscillators. A bandwidth greater than 10 MHz at a carrier frequency of 96 MHz with distortion products 40 dB or greater below desired components has been shown. The distortion behavior as a second-order effect of the loop delay as predicted by analysis has been verified. The output of the inverse-sine phase modulator and its conjugate, generated by a second phase modulator, were subtracted as in a LINC amplifier, to provide at least 40-dB suppression of the zeroth order and even-order components.
Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist (1999)

1. We designed and synthesized several novel cyclic MSH analogues and tested their affinities for cells expressing the MC1, MC3, MC4 and MC5 receptors. 2. One of the substances HS028 (cyclic [AcCys11, dichloro-D-phenylalanine14, Cys18, Asp-NH2(22)]-beta-MSH11-22) showed high affinity (Ki of 0.95nM) and high (80 fold) MC4 receptor selectivity over the MC3 receptor. HS028 thus shows both higher affinity and higher selectivity for the MC4 receptor compared to the earlier first described MC4 receptor selective substance HS014. 3. HS028 antagonised a alpha-MSH induced increase in cyclic AMP production in transfected cells expressing the MC3 and MC4 receptors, whereas it seemed to be a partial agonist for the MC1 and MC5 receptors. 4. Chronic intracerebroventricularly (i.c.v.) administration of HS028 by osmotic minipumps significantly increased both food intake and body weight in a dose dependent manner without tachyphylaxis for a period of 7 days. 5. This is the first report demonstrating that an MC4 receptor antagonist can increase food intake and body weight during chronic administration providing further evidence that the MC4 receptor is an important mediator of long term weight homeostasis.
Synthesis of 8-, 9-, 12-, and 13-mono-13C-retinal (1985)

The 8-, 9-, 12-, and 13-mono- 13 C-retinals were synthesized with &gt; 98% chemical purity and 93% 13 C incorporation from 13 C-labelled acetonitrile. Their 13 C– 13 C and 13 C– 1 H nmr coupling constants were determined.
Absolute conservation of residue 6 of immunoglobulin heavy chain variable regions of class IIA is required for correct folding (1998)

While studying the expression of single-chain antibodies (scFv) derived from several murine monoclonal antibodies, we found that residue 6 in Framework region 1 of the heavy chain variable domain plays a crucial role in antibody folding. Binding activity of three murine antibodies with a heavy chain variable region (VH) subgroup IIA was completely lost when at this position the wild-type residue glutamine (Q) was substituted by glutamate (E). Increased sensitivity towards trypsin digestion of soluble scFv suggested that the lack of binding activity was caused by incorrect folding of Q6E mutants. Grafting of the three additional class IA derived FR1 residues, based upon the comparison between both classes of VH sequences, on to the 'defect' subgroup IIA sequence, partially restored the antigen binding activity of the Q6E-containing scFv. Our results suggest that residue 6 of the heavy chain may be part of a folding nucleus, involving the first two beta-strands of Framework region 1. The evolutionary conservation of either glutamine or glutamate at position 6 in different antibody families may well indicate that within immunoglobulin VH domains, different family specific folding nuclei have evolved.
Inhibition of HIV-1 replication by ribozymes that show poor activityin vitro (1993)

Self-cleaving RNAs (ribozymes) can be engineered to cleave target RNAs of choice in a sequence-specific manner (1). Consequently, they could be used to inhibit virus replication or to analyse host gene function in vivo. However, ribozymes that are catalytic in vitro are generally disappointing when analysed in cells unless expressed at high levels relative to their target RNAs (2, 3). Here we provide evidence that this can be overcome by optimizing ribozyme structure using cellular rather than cell-free assays. We show that ribozymes of relatively long flanking complementary regions (FCRs), while poor catalysts in vitro, can produce profound inhibition of HIV replication in cells. By examining a series of ribozymes in which the FCRs vary from 9 to 564 nucleotides, we establish that the optimum length for activity in the cell is > or = 33 nucleotides.
Removing the costs of indirection in flash-based SSDs with nameless writes (2010)

We present nameless writes, a new interface that obviates the need for indirection in modern solid-state storage devices (SSDs). Nameless writes allow the device to pick the location of a write and only then inform the client above of the decision. Doing so keeps control of block allocation decisions in the device, thus enabling it to perform important tasks such as wear-leveling, while removing the need for large and costly indirection tables. We discuss the proposed interface as well as the requisite device and file-system support. 1
Basic Helix-Loop-Helix Transcription Factor Profiling of Lung Tumors Shows Aberrant Expression of the Proneural Gene Atonal Homolog 1 (ATOH1, HATH1, MATH1) in Neuroendocrine Tumors (2007)

Microarray-based expression profiling studies of lung adenocarcinomas have defined neuroendocrine subclasses with poor prognosis. As neuroendocrine development is regulated by members of the achaetescute and atonal classes of basic helix-loop-helix (bHLH) transcription factors, we analyzed lung tumors for expression of these factors. Out of 13 bHLH genes tested, 4 genes, i.e., achaetescute complex-like 1 (ASCL1, HASH1, Mash1), atonal homolog 1 (ATOH1, HATH1, MATH1), NEUROD4 (ATH-3, Atoh3, MATH-3) and neurogenic differentiation factor 1 (NEUROD1, NEUROD, BE-TA2), showed differential expression among lung tumors and absent or low expression in normal lung. As expected, tumors that have high levels of ASCL1 also express neuroendocrine markers, and we found that this is accompanied by increased levels of NEUROD1. In addition, we found ATOH1 expression in 9 (16%) out of 56 analyzed adenocarcinomas and these tumors showed neuroendocrine features as shown by dopa decarboxylase mRNA expression and immunostaining for neuroendocrine markers. ATOH1 expression as well as NEUROD4 was observed in small cell lung carcinoma (SCLC), a known neuroendocrine tumor. Since ATOH1 is not known to be involved in normal lung development, our results suggest that aberrant activation of ATOH1 leads to a neuroendocrine phenotype similar to what is observed for ASCL1 activation during normal neuroendocrine development and in lung malignancies. Our preliminary data indicate that patients with ATOH1-expressing adenocarcinomas might have a worse prognosis.
Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats (2014)

Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40 μg/kg) and buprenorphine (20 μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry. Plasma concentration-time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration-time curve (AUC) and the maximum plasma concentrations (Cmax ) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.
The Use of the Polymerase Chain Reaction and the Detection of Amplified Products (2003)

The most polymorphic genetic markers are DNA regions composed of variable number tandem repeats (VNTRs) (1,2). Detection of the various VNTRs is possible by restriction fragment-length polymorphism (RFLP) analysis using the Southern blot procedure (3). However, this procedure is time-consuming and requires an isotopic assay to achieve the sensitivity necessary to detect VNTR alleles in samples containing as little as 10-50 ng of human DNA (4). The inability of RFLP technology to resolve discretely the alleles of VNTR loci also is a limitation. Where only limited quantities of DNA are available, or only single copy loci are to be analyzed, the DNA profile may be too weak to be detected with general RFLP methodology.
Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. (1983)

We devised a new method for examining the structural changes that occur in trabecular bone in aging and in osteoporosis. With simultaneous measurement of total perimeter and bone area in thin sections, indirect indices of mean trabecular plate thickness (MTPT) and mean trabecular plate density (MTPD) can be derived, such that trabecular bone volume = MTPD X MTPT. MTPD is an index of the probability that a scanning or test line will intersect a structural element of bone, and is the reciprocal of the mean distance between the midpoints of structural elements, multiplied by pi/2. We applied this method to iliac bone samples from 78 normal subjects, 100 patients with vertebral fracture, and 50 patients with hip fracture. The reduction in trabecular bone volume observed in normal subjects with increasing age was mainly due to a reduction in plate density, with no significant decrease in plate thickness. The further reduction in trabecular bone volume observed in patients with osteoporotic vertebral fracture was mainly due to a further reduction in plate density. There was a relatively smaller reduction in plate thickness that was statistically significant in males but not in females. Only in patients with hip fracture did trabecular thinning contribute substantially to the additional loss of trabecular bone in osteoporosis relative to age. These data indicate that age-related bone loss occurs principally by a process that removes entire structural elements of bone; those that remain are more widely separated and some may undergo compensatory thickening, but most slowly become reduced in thickness. We propose that the process of removal is initiated by increased depth of osteoclastic resorption cavities which leads to focal perforation of trabecular plates; this is followed by progressive enlargement of the perforations with conversion of plates to rods. The resulting structural changes are more severe in osteoporotic patients than in normal subjects, but have been completed in most patients before they develop symptoms.
Molecular and Cellular Mechanisms of Myocardial Failure (1997)

Myocardial remodeling is a central feature in the progression of myocardial failure. This process, which can be stimulated by factors that are increased as a result of myocardial dysfunction such as mechanical stress, angiotensin, and norepinephrine, consists of a variety of molecular and cellular events that can lead to important changes in myocardial structure and function (or phenotype). These alterations include hypertrophy and cellular apoptosis of myocytes, changes in the molecular phenotype of the myocardium with reinduction of a fetal gene program, and alterations in the quantity and composition of the extracellular matrix. Agents that counteract these factors, such as vasodilators, angiotensin-converting enzyme inhibitors, and beta-adrenergic antagonists, slow the progression of myocardial failure and are of clinical value in the treatment of heart failure. Several additional mechanisms have recently been identified that could also be important in mediating myocardial remodeling. These include oxidative stress, inflammatory cytokines, nitric oxide, endothelin, and peptide growth factors. It is likely that additional strategies to inhibit these mechanisms will exert beneficial effects on the process of myocardial remodeling and the development of clinical heart failure.
A Method for Evaluating both Non-Narcotic and Narcotic Analgesics (1957)

A simple method has been designed for evaluating both non-narcotic and narcotic analgesics. The method is based upon the specific antagonism of analgesics to the typical “syndrome” produced by intra-peritoneal injection of 2-phenyl-1,4-benzo-quinone in mice. The antagonism occurs at doses far below those producing depression or other toxic effects. There is also a good correlation between clinical efficacy of a number of analgesics and their relative potency as established by this method. The endpoint is sharp, and the method is simple and quantitative.