gebhart/patrepeval huggingface dataset:
Genetic Engineering of Algae for Enhanced Biofuel Production (2010)

There are currently intensive global research efforts aimed at increasing and modifying the accumulation of lipids, alcohols, hydrocarbons, polysaccharides, and other energy storage compounds in photosynthetic organisms, yeast, and bacteria through genetic engineering. Many improvements have been realized, including increased lipid and carbohydrate production, improved H(2) yields, and the diversion of central metabolic intermediates into fungible biofuels. Photosynthetic microorganisms are attracting considerable interest within these efforts due to their relatively high photosynthetic conversion efficiencies, diverse metabolic capabilities, superior growth rates, and ability to store or secrete energy-rich hydrocarbons. Relative to cyanobacteria, eukaryotic microalgae possess several unique metabolic attributes of relevance to biofuel production, including the accumulation of significant quantities of triacylglycerol; the synthesis of storage starch (amylopectin and amylose), which is similar to that found in higher plants; and the ability to efficiently couple photosynthetic electron transport to H(2) production. Although the application of genetic engineering to improve energy production phenotypes in eukaryotic microalgae is in its infancy, significant advances in the development of genetic manipulation tools have recently been achieved with microalgal model systems and are being used to manipulate central carbon metabolism in these organisms. It is likely that many of these advances can be extended to industrially relevant organisms. This review is focused on potential avenues of genetic engineering that may be undertaken in order to improve microalgae as a biofuel platform for the production of biohydrogen, starch-derived alcohols, diesel fuel surrogates, and/or alkanes.
SCANNING ELECTRON MICROSCOPY OF THE STRATUM CORNEUM (1972)

Summary.— This report describes studies of stratum corneum from normal subjects and from patients with various scaly disorders, with the scanning electron microscope, using the skin surface biopsy technique. Normnal squamous cells showed essentially the same structure in different parts of the body; individual squames demonstrated irregular surface folds, convolutions and occasionally a more villous appearance. In dominant ichthyosis vulgaris the squamous cells showed predominantly an irregular fine nodular surface pattern. Similar changes were found in non-bullous ichthyosiform erythroderma. Surface depressions (maxitnum diameter approximately 300 nm) were occasionally seen on squames from bullous ichthyosiform erythroderma. Psoriatic squamous cells showed a more pronounced villous pattern than normal squames, the villi being evenly distributed over the surface of the majority of cells examined; some cells had rather flattened villi near their edges. Possible physiological roles for the structural changes found are discussed.
Induction of Tumor Cell Apoptosis In Vivo Increases Tumor Antigen Cross-Presentation, Cross-Priming Rather than Cross-Tolerizing Host Tumor-Specific CD8 T Cells (2003)

Cross-presentation of cell-bound Ags from established, solid tumors to CD8 cells is efficient and likely to have a role in determining host response to tumor. A number of investigators have predicted that when tumor Ags are derived from apoptotic cells either no response, due to Ag "sequestration," or CD8 cross-tolerance would ensue. Because the crucial issue of whether this happens in vivo has never been addressed, we induced apoptosis of established hemagglutinin (HA)-transfected AB1 tumors in BALB/c mice using the apoptosis-inducing reagent gemcitabine. This shrank the tumor by approximately 80%. This induction of apoptosis increased cross-presentation of HA to CD8 cells yet neither gross deletion nor functional tolerance of HA-specific CD8 cells were observed, based on tetramer analysis, proliferation of specific CD8 T cells, and in vivo CTL activity. Interestingly, apoptosis primed the host for a strong antitumor response to a second, virus-generated HA-specific signal in that administration of an HA-expressing virus after gemcitabine administration markedly decreased tumor growth compared with viral administration without gemcitabine. Thus tumor cell apoptosis in vivo neither sequesters tumor Ags nor cross-tolerizes tumor-specific CD8 cells. This observation has fundamental consequences for the development of tumor immunotherapy protocols and for understanding T cell reactivity to tumors and the in vivo immune responses to apoptotic cells.
Superconducting persistent-current qubit (1999)

We present the design of a superconducting qubit that has circulating currents of opposite sign as its two states. The circuit consists of three nanoscale aluminum Josephson junctions connected in a superconducting loop and controlled by magnetic fields. The advantages of this qubit are that it can be made insensitive to background charges in the substrate, the flux in the two states can be detected with a superconducting quantum interference device, and the states can be manipulated with magnetic fields. Coupled systems of qubits are also discussed as well as sources of decoherence.
Asymmetric Bessel–Gauss beams (2014)

We propose a three-parameter family of asymmetric Bessel-Gauss (aBG) beams with integer and fractional orbital angular momentum (OAM). The aBG beams are described by the product of a Gaussian function by the nth-order Bessel function of the first kind of complex argument, having finite energy. The aBG beam's asymmetry degree depends on a real parameter c≥0: at c=0, the aBG beam is coincident with a conventional radially symmetric Bessel-Gauss (BG) beam; with increasing c, the aBG beam acquires a semicrescent shape, then becoming elongated along the y axis and shifting along the x axis for c≫1. In the initial plane, the intensity distribution of the aBG beams has a countable number of isolated optical nulls on the x axis, which result in optical vortices with unit topological charge and opposite signs on the different sides of the origin. As the aBG beam propagates, the vortex centers undergo a nonuniform rotation with the entire beam about the optical axis (c≫1), making a π/4 turn at the Rayleigh range and another π/4 turn after traveling the remaining distance. At different values of the c parameter, the optical nulls of the transverse intensity distribution change their position, thus changing the OAM that the beam carries. An isolated optical null on the optical axis generates an optical vortex with topological charge n. A vortex laser beam shaped as a rotating semicrescent has been generated using a spatial light modulator.
The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid β protein ending at the 42nd (or 43rd) residue (1997)

To gain insights into the significance of presenilins (PS) in the pathogenetic mechanisms of early-onset familial Alzheimer disease (FAD), we expressed cDNAs for wild-type PS2 and PS2 with the Volga German (N141I) mutation in cultured cells and then examined the metabolism of the transfected proteins and their effect on the C-terminal properties of secreted amyloid beta protein (A beta). PS2 was identified as a 50- to 55-kDa protein, which was cleaved to produce N-terminal fragments of 35-40 kDa and C-terminal fragments of 19-23 kDa. The Volga German (N141I) mutation did not cause any significant change in the metabolism of PS2. COS-1 cells doubly transfected with cDNAs for N141I mutant PS2 and human beta-amyloid precursor protein (betaAPP) or a C-terminal fragment thereof, as well as mouse Neuro2a neuroblastoma cells stably transfected with N141I mutant PS2 alone, secreted 1.5- to 10-fold more A beta ending at residues 42 (or 43) [A beta42(43)] compared with those expressing the wild-type PS2. These results strongly suggest that the PS2 mutation (N141I) linked to FAD alters the metabolism of A beta/betaAPP to foster the production of the form of A beta that most readily deposits in amyloid plaques. Thus, mutant PS2 may lead to AD by altering the metabolism of A beta/betaAPP.
Production of homozygous mutant ES cells with a single targeting construct. (1992)

We have developed a simple method for producing embryonic stem (ES) cell lines whereby both alleles have been inactivated by homologous recombination and which requires a single targeting construct. Four different ES cell lines were created that were heterozygous for genes encoding two guanine nucleotide-binding protein subunits, alpha i2 and alpha i3, T-cell receptor alpha, and beta-cardiac myosin heavy chain. When these heterozygous cells were grown in high concentrations of G418, many of the surviving cells were homozygous for the targeted allele and contained two copies of the G418 resistance gene. This scheme provides an easy method for obtaining homozygous mutationally altered cells, i.e., double knockouts, and should be generally applicable to other genes and to cell lines other than ES cells. This method should also enable the production of cell lines in which more than one gene have had both alleles disrupted. These mutant cells should provide useful tools for defining the role of particular genes in cell culture.
Improving nutrition and physical activity in the workplace: a meta-analysis of intervention studies (2011)

A comprehensive search of the literature for studies examining physical activity or nutrition interventions in the workplace, published between 1999 and March 2009, was conducted. This search identified 29 relevant studies. Interventions were grouped according to the theoretical framework on which the interventions were based (e.g. education, cognitive-behavioural, motivation enhancement, social influence, exercise). Weighted Cohen's d effect sizes, percentage overlap statistics, confidence intervals and fail safe Ns were calculated. Most theoretical approaches were associated with small effects. However, large effects were found for some measures of interventions using motivation enhancement. Effect sizes were larger for studies focusing on one health behaviour and for randomized controlled trials. The workplace is a suitable environment for making modest changes in the physical activity, nutrition and health of employees. Further research is necessary to determine whether these changes can be maintained in the long term.
GnRH Antagonists:  A New Generation of Long Acting Analogues Incorporatingp-Ureido-phenylalanines at Positions 5 and 6 (2000)

A series of antagonists of gonadotropin-releasing hormone (GnRH) of the general formula Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph/4Amf(P)-D4Aph/D4Amf(Q)-Leu-ILys-Pro-DAla-NH2 was synthesized, characterized, and screened for duration of inhibition of luteinizing hormone release in a castrated male rat assay. Selected analogues were tested in a reporter gene assay (IC50 and pA2) and an in vitro histamine release assay. P and Q contain urea/carbamoyl functionalities designed to increase potential intra- and intermolecular hydrogen bonding opportunities for structural stabilization and peptide/receptor interactions, respectively. These substitutions resulted in analogues with increased hydrophilicity and a lesser propensity to form gels in aqueous solution than azaline B [Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(Atz)-D4Aph(Atz)-Leu-ILys-Pro-DAla-NH2 with Atz = 3'-amino-1H-1',2',4'-triazol-5'-yl, 5], and in some cases they resulted in a significant increase in duration of action after subcutaneous (s.c.) administration. Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(L-hydroorotyl)-D4Aph(carbamoyl)-Leu-ILys-Pro-DAla-NH2 (acetate salt is FE200486) (31) and eight other congeners (20, 35, 37, 39, 41, 45-47) were identified that exhibited significantly longer duration of action than acyline [Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(Ac)-D4Aph(Ac)-Leu-ILys-Pro-DAla-NH2] (6) when administered subcutaneously in castrated male rats at a dose of 50 microg in 100 microL of phosphate buffer. No correlation was found between retention times on a C18 reverse phase column using a triethylammonium phosphate buffer at pH 7.0 (a measure of hydrophilicity) or affinity in an in vitro human GnRH report gene assay (pA2) and duration of action. FE200486 was selected for preclinical studies, and some of its properties were compared to those of other clinical candidates. In the intact rat, ganirelix, abarelix, azaline B, and FE200486 inhibited plasma testosterone for 1, 1, 14, and 57 days, respectively, at 2 mg/kg s.c. in 5% mannitol (injection volume = 20 microL). Based on the information that 31, 33, 35 and 37 were significantly shorter acting than acyline or azaline B after intravenous administration (100 microg/rat), we surmised that the very long duration of action of the related FE200486 (for example) was likely due to unique physicochemical properties such as solubility in aqueous milieu, comparatively low propensity to form gels, and ability to diffuse at high concentrations in a manner similar to that described for slow release formulations of peptides. Indeed, in rats injected s.c. with FE200486 (2 mg/kg), plasmatic concentrations of FE200486 remained above 5 ng/mL until day 41, and the time after which they dropped below 3 ng/mL and plasma LH levels started rising until full recovery was reached at day 84 with levels of FE200486 hovering around 1 ng/mL. Additionally, FE200486 was less potent at releasing histamine from isolated rat mast cells than any of the GnRH antagonists presently described in preclinical reports.
Simple and Scalable Gel-Based Separation of Metallic and Semiconducting Carbon Nanotubes (2009)

We report a rapid and scalable method for the separation of metallic and semiconducting single-wall carbon nanotubes (SWCNTs); the separation is performed by the selective adsorption of semiconducting SWCNTs on agarose gel. The most effective separation was realized by a simple procedure in which a piece of gel containing SWCNTs and sodium dodecyl sulfate was frozen, thawed, and squeezed. This process affords a solution containing 70% pure metallic SWCNTs and leaves a gel containing 95% pure semiconducting SWCNTs. Field-effect transistors constructed from the separated semiconducting SWCNTs have been demonstrated to function without any electrical breakdown.
Clinical Significance of Squamous Cell Carcinoma Antigen in Cancer of the Human Uterine Cervix (1991)

Serum squamous cell carcinoma antigen (SCCa) concentrations were determined by a radioimmunoassay kit before and during the treatment of 50 patients with cervical carcinoma: 44 with squamous cell carcinoma (SCC) and 6 with adenocarcinoma. The positivity rate of SCCa was 50% (52% for SCC and 33% for adenocarcinoma). The sensitivity of SCCa for SCC was twice as high as that of CEA and CA-125. Low serum concentrations were observed in early-stage carcinoma, indicating that SCCa is not useful for diagnosis. In advanced cases, serum levels were directly and significantly correlated with the stage of the disease.
Efficient Discovery of Potent Anti-HIV Agents Targeting the Tyr181Cys Variant of HIV Reverse Transcriptase (2011)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the replication of human immunodeficiency virus (HIV) are being pursued with guidance from molecular modeling including free-energy perturbation (FEP) calculations for protein-inhibitor binding affinities. The previously reported pyrimidinylphenylamine 1 and its chloro analogue 2 are potent anti-HIV agents; they inhibit replication of wild-type HIV-1 in infected human T-cells with EC(50) values of 2 and 10 nM, respectively. However, they show no activity against viral strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. Modeling indicates that the problem is likely associated with extensive interaction between the dimethylallyloxy substituent and Tyr181. As an alternative, a phenoxy group is computed to be oriented in a manner diminishing the contact with Tyr181. However, this replacement leads to a roughly 1000-fold loss of activity for 3 (2.5 μM). The present report details the efficient, computationally driven evolution of 3 to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C-containing variants. The critical contributors were FEP substituent scans for the phenoxy and pyrimidine rings and recognition of potential benefits of addition of a cyanovinyl group to the phenoxy ring.
DICED CARTILAGE GRAFTS: NEW METHOD FOR REPAIR OF SKULL DEFECTS, MASTOID FISTULA AND OTHER DEFORMITIES (1943)

In 1938 I reported on the operative repair of deep depressions in the frontal region of the skull in 15 patients. The depressions were filled with segments of autogenous rib cartilage, inserted one above the other, as illustrated in figure 1. These patients presented normally rounded skull contours until about two months after the operation, but from this time on irregularities developed which outlined the separate rib cartilage segments. The irregularities were most noticeable when an extensive depression had been repaired. Secondary operations in which projecting portions of cartilage were removed served to improve the line of the forehead, but did not completely correct the irregularities. Some immediate improvement was also obtained by introduction of sheets of dermal graft between the cartilage and the overlying skin of the scalp, but the late results were disappointing. Depressions in the skull repaired by insertion of bone grafts likewise present postoperative irregularities, similar
Acidic Fibroblast Growth Factor (aFGF) in Developing Normal and Dystrophic (mdx) Mouse Muscles. Distribution in Degenerating and Regenerating mdx Myofibres (1992)

Affinity purified polyclonal antibodies directed against human recombinant acidic FGF (aFGF), were used in immunofluorescence studies to localize this growth factor in several normal and dystrophic (mdx) mouse skeletal muscles. The expression of aFGF was detected throughout the life of both the control and mdx mice. In striated muscles, examined up to 3 weeks postnatal, aFGF was localized around the myofibres and this pattern was consistent in both mdx and the normal counterpart strain. However, the intensity of the signal was much stronger in the mdx strain. In mdx mouse skeletal muscles, examined during the acute phase of degeneration and regeneration (3-14 weeks) aFGF was localized around the myofibres, in approximately 60% of the nuclei of newly formed or regenerated myofibres and also in the pockets of necrosis which represented actively degenerating myofibres. In normal mouse skeletal muscles, studied over the same period, the antibodies localized aFGF mainly to the periphery of the muscle fibres. The augmentation of aFGF observed by immunofluorescence in mdx mouse muscles was confirmed by enzyme immunoassay (EIA) analysis of the same muscles over the same period of time. The data from the EIA indicated a 3.5-fold increase in aFGF in mdx as compared to normal muscles at 3 weeks, and an approximate 26-fold increase during the period of active degeneration-regeneration. This increased concentration of aFGF noted in the mdx muscles suggests that this endogenous aFGF may participate in the high level of regenerative activity observed in mdx mouse.
ENDOSCOPIC THERAPY FOR BARRETT’S OESOPHAGUS (2005)

Barrett’s oesophagus or columnar lined oesophagus is among the most intriguing of gastroenterological conditions. This is because of its pathogenesis, prevalence, association with reflux disease, male sex and, in particular, the potential for neoplastic degeneration to adenocarcinoma. The current and dramatic rise in the incidence of oesophageal adenocarcinoma is centred on the UK (5–8.7/100 000), over double that of the USA (3.7/100 0000). This epidemic is fairly localised and is not evident in Asia, where squamous cell cancer remains the predominant oesophageal malignancy. Large rises in incidence, up to 30% per year, have been seen in West European White men, a rise not mirrored in Eastern Europe.1,2

At present the incidence remains paralleled by mortality. The prognosis of oesophageal cancer remains universally poor; median survival has hardly changed from 0.75 years between 1973 and 1977 to 0.9 years between 1993 and 1999. This almost trivial change has led some to suggest that the change could be accounted for by improved reporting and detection bias rather than any important therapeutic advance.3

Gradual malignant degeneration within a segment of Barrett’s oesophagus occurs in a probabilistic rather than in a deterministic manner. Barrett’s appears to be a necessary intermediary step. The relatively long time sequence to cancer may allow early intervention with endoscopic ablation, thus offering the possibility of preventing the lethal development of symptomatic oesophageal adenocarcinoma. Stark choices face patient and clinician in the presence of a degenerating “possibly” premalignant Barrett’s mucosa. Radical therapy offers an overaggressive, “possibly” flawed approach if the diagnosis and prognosis remain uncertain. It cannot be considered a triumph to have a millimetre of worrying but superficial disease and remove a whole oesophagus. The alternative of surveillance presents other concerns. It offers intermittent endoscopic inspection at proscribed, economically viable, and societal designated intervals, and awaits …
PCR-based landmark unique gene (PLUG) markers effectively assign homoeologous wheat genes to A, B and D genomes (2007)

In the development of wheat EST-PCR markers capable of efficiently sorting products derived from homoeologous genes, it is important to design primers able to amplify products that include intron sequences with insertion/deletion polymorphisms. Using the PLUG system, wheat EST sequences that can be used for marker development are selected based on comparative genomics with rice, and then primer sets flanking intron sequences are prepared in an interactive, semi-automatic manner. Hence, the PLUG system is an effective tool for large-scale marker development.
The δ subunit of AP-3 is required for efficient transport of VSV-G from the trans-Golgi network to the cell surface (2002)

Vesicular stomatitis virus glycoprotein (VSV-G) is a transmembrane protein that functions as the surface coat of enveloped viral particles. We report the surprising result that VSV-G uses the tyrosine-based di-acidic motif (-YTDIE-) found in its cytoplasmic tail to recruit adaptor protein complex 3 for export from the trans-Golgi network. The same sorting code is used to recruit coat complex II to direct efficient transport from the endoplasmic reticulum to the Golgi apparatus. These results demonstrate that a single sorting sequence can interact with sequential coat machineries to direct transport through the secretory pathway. We propose that use of this compact sorting domain reflects a need for both efficient endoplasmic reticulum export and concentration of VSV-G into specialized post-trans-Golgi network secretory-lysosome type transport containers to facilitate formation of viral coats at the cell surface.
Historical Development of the Dopamine Hypothesis of Schizophrenia (2002)

This review examines the history of discoveries that contributed to development of the dopamine hypothesis of schizophrenia. The origin of the hypothesis is traced to the recognition that neuroleptic drugs interfere with brain dopamine function. This insight was derived from two distinct lines of research. The first line originated from the discovery in 1956 that reserpine depletes brain serotonin. This finding resulted in a sequence of studies that led to the discovery that brain dopamine is involved in neuroleptic-induced extrapyramidal motor disturbances. The second line of research was aimed at determining the mechanism of action of psychomotor stimulants. This research produced evidence that stimulants directly or indirectly activate brain dopamine receptors. Because nonreserpine neuroleptics such as chlorpromazine block stimulant-induced movement, these findings suggested that neuroleptics were dopamine antagonists. Most previous accounts of the development of the dopamine hypothesis of schizophrenia emphasize the first line of research and ignore the second.