gebhart/patrepeval huggingface dataset:
Promoters from Genes for Plastid Proteins Possess Regions with Different Sensitivities toward Red and Blue Light (1994)

The light-regulated expression of eight nuclear-encoded genes for plastid proteins from spinach (Spinacia oleracea) (RBCS-1 and CAB-1; ATPC and ATPD, encoding the subunits gamma and delta of the ATP synthase; PC and FNR; PSAD and PSAF, encoding the subunits II and III of photosystem I reaction center) was analyzed with promoter/beta-glucuronidase (GUS) gene fusions in transgenic tobacco (Nicotiana tabacum and Nicotiana plumbaginifolia) seedlings and mature plants under standardized light and growth conditions. Unique response patterns were found for each of these promoters. GUS activities differed more than 30-fold. Strong promoters were found for the PC and PSAD genes. On the other hand, the ATPC promoter was relatively weak. Expression of the CAB/GUS gene fusion in etiolated material was at the detection limit; all other chimeric genes were expressed in the dark as well. Light stimulation of GUS activities ranged from 3- (FNR promoter) to more than 100-fold (CAB-1 promoter). The FNR promoter responded only to red light (RL) and not significantly to blue light (BL), whereas the PC promoter contained regions with different sensitivities toward RL and BL. Furthermore, different RNA accumulation kinetics were observed for the PSAF, CAB, FNR, and PC promoter/GUS gene fusions during de-etiolation, which, at least in the case of the PSAF gene, differed from the regulation of the corresponding endogenous genes in spinach and tobacco. The results suggest either that not all cis elements determining light-regulated and quantitative expression are present on the spinach promoter fragments used or that the spinach cis-regulatory elements respond differently to the host (tobacco) regulatory pathway(s). Furthermore, as in tobacco, but not in spinach, the trans-gene hardly responds to single light pulses that operate through phytochrome. Taken together, the results suggest that the genes have been independently translocated from the organelle to the nucleus during phylogeny. Furthermore, each gene seems to have acquired a unique set of regulatory elements.
High-performance p-i-n Ge on Si photodetectors for the near infrared: from model to demonstration (2001)

We have investigated the integration of Ge p-i-n and n-i-p heterojunction photodiodes on Si. Recognizing the crucial role of interface defects at the Ge-Si interface on the performance of photodetectors, we have designed and fabricated high-performance n-i-p Ge photodiodes on p/sup +/-Si substrates. These photodiodes exhibit short-circuit responsivities of 0.3 and 0.2 A/W at 1.3 and 1.55 /spl mu/m, respectively, reverse dark currents of 20 mA/cm/sup 2/ and response times of 800 ps.
Human prostatic carcinoma: an electron microscope study. (1966)

Electron microscopic studies of human prostatic cancers revealed that cytologically well-differentiated and poorly differentiated tumor cells are present in both histologically well-differentiated and anaplastic prostatic cancers. Secretory and enzyme (acid phosphatase) activity in the cancer cell is dependent on cytologic differentiation; the latter bears no constant relation to histologic differentiation of the tumor. The amount of well-differentiated tumor cells in a given cancer determines the degree and intensity of acid phosphatase activity in the tumor. The presence of poorly differentiated tumor cells and their generally diminished secretory activity account for the diminished acid phosphatase activity (histochemically and biochemically) often observed in prostatic cancers.

Basement membranes are present, although often incompletely, around the cancer acinus and even around individual cancer cells.

Outstanding features of prostatic cancer cells, when compared to normal and hyperplastic prostatic epithelial cells, are the nuclear hypertrophy, hyperchromatinism, nucleolar hypertrophy, increase in number and pleomorphism of mitochondria, greater amount of free ribosomes, variability of position of Golgi apparatus, and increased amount of lipid droplets of variable morphology. The significance of these features, and the differentiation of cancer cells in relation to production and secretion, particularly that of acid phospatases and its level in the serum, are discussed.
Long-term follow-up including extensive complement analysis of a pediatric C3 glomerulopathy cohort (2021)

We extensively described clinical and laboratory findings including complement features of an exclusively pediatric C3G cohort. Outcome was relatively benign, persistent low C3 correlated with C3NeF presence, and C3GN was associated with higher sC5b-9 and lower properdin levels. Prospective studies are needed to further elucidate the pathogenic mechanisms underlying C3G and guide personalized medicine with complement therapeutics.
The POU Domain of SCIP/Tst-1/Oct-6 Is Sufficient for Activation of an Acetylcholine Receptor Promoter (1996)

In the PC12 neuroendocrine line, the neuronal nicotinic acetylcholine receptor alpha3 gene promoter is activated by SCIP/Tst-1/Oct-6, a POU domain transcription factor proposed to be important for regulating the development of specific neural cell populations. In this study, we have investigated the SCIP polypeptide domains involved in alpha3 promoter activation. The characteristics of activation by a chimeric effector in which the GAL4 DNA binding domain was substituted for the SCIP POU domain were dramatically different from those of wild-type SCIP. At low effector masses, the chimeric polypeptide weakly activated alpha3 in a GAL4 binding-site-dependent manner but then squelched transcription at higher masses. In contrast, wild-type SCIP activation was not modulated by the presence of multimerized SCIP binding sites, and squelching was not observed. Analysis of wild-type SCIP truncations revealed that deletion of the previously characterized SCIP amino-terminal activation domain did not destroy activity of the factor. Surprisingly, a truncation expressing nothing more than the POU domain was nearly as active as wild-type SCIP. Moreover, cotransfection of a GAL4-VP16 effector with an effector expressing just the SCIP POU domain resulted in synergistic activation of the promoter. Synergistic activation did not depend on an Sp1 motif that is the only functional alpha3 cis element outside the transcription start site region. Our results show that the DNA binding domain of a POU factor is capable of transcriptional activation probably through protein-protein interactions with components of the basal transcription complex.
Randomized Prospective Trial of Continuous vs Intermittent Heparin Therapy (1976)

Forty-one patients with clinical indications for heparin therapy were randomized to receive continuous intravenous heparin sodium therapy or intermittent (four-hourly bolus) heparin therapy, with control by the activated partial thromboplastin time. Seven of 21 patients receiving intermittent therapy had major bleeding episodes, whereas none of the 20 patients receiving continuous heparin therapy had major bleeding (P = .005). One patient on continuous therapy had a pulmonary embolus, while none on intermittent therapy had recurrent thromboembolism. Two heavily bleeding patients on intermittent therapy were switched to continuous treatment after bleeding was controlled. The use of continuous heparin therapy appears significantly safer with regard to hemorrhagic complications than the use of intermittent therapy.
Roles of trpE2, entC and entD in salicylic acid biosynthesis in Mycobacterium smegmatis (2010)

Mycobacterium smegmatis acquires extracellular iron using exochelin, mycobactin and carboxymycobactin. The latter two siderophores are synthesized from salicylic acid, which, in turn, is derived from chorismic acid in the shikimic acid pathway. To understand the conversion mechanism of chorismic acid to salicylic acid in M. smegmatis, knockout mutants of the putative key genes, trpE2, entC and entD, were created by targeted mutagenesis. By enzymatic assays with the cell-free extracts of the various knockout mutants, we have shown that TrpE2 converts chorismic acid into isochorismic acid and is thus an isochorismate synthase. The gene products of both entC and entD are involved in the conversion of isochorismic acid into salicylic acid, and hence correspond to salicylate synthase.
Thrombin Generation Assay and Its Application in the Clinical Laboratory (2016)

From my analysis of the literature, I draw the following conclusions. There is strong evidence that TGA is helpful to elucidate coagulation mechanisms in various clinical conditions that until recently were poorly understood (chronic liver disease; diabetes; inflammatory bowel disease, myeloproliferative neoplasms, nonalcoholic fatty liver disease). TGA is a promising laboratory tool for investigating hemorrhagic coagulopathies and monitoring replacement therapy in hemophiliacs, predicting the risk of recurrent venous thromboembolism after a first event, and monitoring patients on parenteral or oral anticoagulants. These applications require clinical trials in which TGA results are combined with specific clinical end points.
Specific Down-regulation of HER-2/neu Mediated by a Chimeric U6 Hammerhead Ribozyme Results in Growth Inhibition of Human Ovarian Carcinoma (2001)

The U6 expression system was explored for efficient expression of a ribozyme against the human proto-oncogene c-neu. A hammerhead ribozyme (neuRz) and the control mutant ribozyme (MRz) were targeted to cleave c-neu mRNA at the tyrosine kinase domain. In vitro cleavage showed that neuRz was very active while MRz was not. Near-maximal target cleavage observed at a low ribozyme:target ratio (0.1) suggests that neuRz has good activity and turnover capability under physiological conditions, i.e., <5 mM MgCl(2) and 37 degrees C. Chimeric U6 ribozyme was expressed at about 5 x 10(6) copies/cell at 48 h in the ovarian carcinoma cell line SKOV-3.ip1. Partial down-regulation of c-neu mRNA and protein was observed in a dose-dependent manner in cells transiently transfected with U6neuRz- but not with MRz-containing plasmid. Sorted transient transfectants demonstrated dramatic growth inhibition with the neuRz-expressing cells. Our results demonstrate that the U6 expression system is very efficient and suitable for the expression of a hammerhead ribozyme. Moreover, nonviral delivery of the neuRz-expressing plasmid resulted in specific down-regulation of c-neu and, subsequently, growth inhibition of ovarian cancer cells overexpressing c-neu.
Structural insights into diversity and n-alkane biodegradation mechanisms of alkane hydroxylases (2013)

Environmental microbes utilize four degradation pathways for the oxidation of n-alkanes. Although the enzymes degrading n-alkanes in different microbes may vary, enzymes functioning in the first step in the aerobic degradation of alkanes all belong to the alkane hydroxylases. Alkane hydroxylases are a class of enzymes that insert oxygen atoms derived from molecular oxygen into different sites of the alkane terminus (or termini) depending on the type of enzymes. In this review, we summarize the different types of alkane hydroxylases, their degrading steps, and compare typical enzymes from various classes with regard to their three-dimensional structures, in order to provide insights into how the enzymes mediate their different roles in the degradation of n-alkanes and what determines their different substrate ranges. Through the above analyzes, the degrading mechanisms of enzymes can be elucidated and molecular biological methods can be utilized to expand their catalytic roles in the petrochemical industry or in bioremediation of oil-contaminated environments.
HIV-1, lipid rafts, and antibodies to liposomes: implications for anti-viral-neutralizing antibodies (Review) (2006)

The human immunodeficiency virus type 1 (HIV-1) is an enveloped virus with a lipid bilayer that contains several glycoproteins that are anchored in, or closely associated with, the membrane surface. The envelope proteins have complex interactions with the lipids both on the host cells and on the target cells. The processes of budding from host cells and entry into target cells occur at sites on the plasma membrane, known as lipid rafts, that represent specialized regions that are rich in cholesterol and sphingolipids. Although the envelope glycoproteins are antigenic molecules that potentially might be used for development of broadly neutralizing antibodies in a vaccine to HIV-1, the development of such antibodies that have broad specificities against primary field isolates of virus has been largely thwarted to date by the ability of the envelope proteins to evade the immune system through various mechanisms. In this review, the interactions of HIV-1 with membrane lipids are summarized. Liposomes are commonly used as models for understanding interactions of proteins with membrane lipids; and liposomes have also been used both as carriers for vaccines, and as antigens for induction of antibodies to liposomal lipids. The possibility is proposed that liposomal lipids, or liposome-protein combinations, could be useful as antigens for inducing broadly neutralizing antibodies to HIV-1.
Wortmannin and Li+ Specifically Inhibit Clathrin-Independent Endocytic Internalization of Bulk Fluid (1996)

Incubation of a human fibrosarcoma cell line HT-1080 in Li+-containing medium inhibited internalization of a fluid marker, horseradish peroxidase (HRP), by more than 80percnt;. The ion inhibited the activity enhanced by Ca2+ or phorbol 12-myristate 13-acetate. We also found that wortmannin (WT), a potent inhibitor of phosphoinositide (PI) 3-kinase (PI 3-k), inhibited the non-stimulated and the two stimulated types of endocytosis to the same extent as Li+. In contrast, neither WT nor Li+ influenced the early internalization of transferrin (Tfn), EGF or platelet-derived growth factor. Neither targeting to early endosomes nor recycling of the once-internalized Tfn was influenced. When the cytoplasmic pH was lowered by chasing cells that had been preincubated with 25 mM NH4C1 in an amiloride-containing Na+-free medium, more than 90% of internalization of Tfn in HT-1080 cells was inhibited, while that of HBP was reduced by only 34%. In contrast, WT reduced the uptake of HBP by KB cells by 34%, while 60% of the activity was inhibited by the treatment for cytoplasmic acidification. Comparison of other cells i.e., A-549 and a human diploid cell line Miyajima, indicated that cells showing higher sensitivity to WT were less sensitive to low cytoplasmic pH. These results suggest that, in all the cells studied, bulk fluid is internalized either via a clathrin-independent/PI 3-k-dependent route or via a clathrin-dependent/PI 3-k-independent one, though the ratio varied among them. We also found that internalization of a mAb directed toward the 116 (100)-kDa subunit of vacuolar ATPase [0SW2; Sato and Toyama (1994) J. Cell BioL 127, 39–53] in the fluid phase was inhibited by WT, but the antibody was still internalized in a surface-bound form. Regardless of the treatment with WT, most of the antibody was transported to endosomes that were associated with Tfn receptor. These results suggest that both internalization routes are targeted to the same early endosomal compartments.
HIV VACCINES (2005)

A prophylactic vaccine for HIV-1 is badly needed. Despite 20 years of effort, it is still a long way off. However, considerable progress has been made in understanding the problem. The virus envelope has evolved to evade neutralizing antibodies in an extraordinary way, yet a vaccine that can stimulate such antibodies remains the best hope. Anti-HIV-1 T cell responses are evaded by continuous mutation of the virus. Vaccine strategies that concentrate on stimulating T cell immunity will at best generate broadly reactive and persisting T cell responses that can suppress virus without preventing infection, limiting or preventing the damage the virus causes. The SIV macaque models give encouragement that this is possible, but they need further understanding. Therapeutic vaccination should also be considered.
The Prodrug Approach: A Successful Tool for Improving Drug Solubility (2015)

Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug development. This review aims to describe recent advances in the improvement of solubility via the prodrug approach. The main chemical carriers and examples of successful strategies will be discussed, highlighting the advances of this field in the last ten years.
Proton and sodium MRI assessment of emerging tumor chemotherapeutic resistance (2006)

The ultimate goal of any cancer therapy is to target the elimination of neoplastic cells. Although newer therapeutic strategies are in constant development, therapeutic assessment has been hampered by the inability to assess, rapidly and quantitatively, efficacy in vivo. Diffusion imaging and, more recently, sodium MRI have demonstrated their distinct abilities to detect therapy-induced alterations in tumor cellularity, which has been demonstrated to be indicative of therapeutic efficacy. More importantly, both imaging modalities detect tumor response much earlier than traditional methodologies that rely on macroscopic volumetric changes. In this study, the correlation between tumor sodium and diffusion was further tested to demonstrate the sensitivity of sodium imaging to gauge tumor response to therapy by using a 9L rat gliosarcoma treated with varying doses of BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea]. This orthotopic model has been demonstrated to display variability in response to BCNU therapy where initial insult has been shown to lead to drug-resistance. In brief, a single 26.6 mg/kg BCNU dose yielded dramatic responses in both diffusion and sodium MRI. However, a second equivalent BCNU dose yielded a much smaller change in diffusion and sodium, suggesting a drop in tumor sensitivity to BCNU. The MRI responses of animals treated with 13.3 mg/kg BCNU were much lower and similar responses were observed after the initial and secondary applications of BCNU. Furthermore, these results were further validated using volumetric measurements of the tumor and also ex vivo determination of tumor sensitivity to BCNU. Overall, these experiments demonstrate the sensitivity and applicability of sodium and diffusion MRI as tools for dynamic assessment of tumor response to therapy.
A germ cell origin of embryonic stem cells? (2004)

Because embryonic stem (ES) cells are generally derived by the culture of inner cell mass (ICM) cells, they are often assumed to be the equivalent of ICM cells. However, various evidence indicates that ICM cells transition to a different cell type during ES-cell derivation. Historically, ES cells have been believed to most closely resemble pluripotent primitive ectoderm cells derived directly from the ICM. However, differences between ES cells and primitive ectoderm cells have caused developmental biologists to question whether ES cells really have an in vivo equivalent, or whether their properties merely reflect their tissue culture environment. Here, we review recent evidence that the closest in vivo equivalent of an ES cell is an early germ cell.
Ultra low-EOT (5 Å) gate-first and gate-last high performance CMOS achieved by gate-electrode optimization (2009)

A novel gate first integration approach enabling ultra low-EOT is demonstrated. HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> based devices with a zero interface layer and optimized gate-electrode is used to achieve EOT and T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">inv</sub> values of ˜5 Å and ˜8 Å respectively for both n and pMOS devices. The drive currents at I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">off</sub> =100 nA/μm with V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DD</sub> =1 V is 1.4 mA/μm and 0.6 mA/μm (no SiGe source/drain) for n and pMOS respectively. The technology further offers low n/pMOS V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> of 0.3/-0.4V, good V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> -uniformity, and V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> -matching and very high cutoff frequencies at ˜290-340 GHz for 38 nm nMOS devices. A replacement poly gate process is used to further improve upon the pMOS effective work function. TDDB lifetimes over 10 years are reported while BTI indicates potential reliability challenges.
ULS: a versatile method of labeling nucleic acids for FISH based on a monofunctional reaction of cisplatin derivatives with guanine moieties (1999)

The broad extension of an existing chemical DNA labeling technique for molecular cytogenetics is described. Called the Universal Linkage System (ULS(TM)), it is based on the capability of monoreactive cisplatin derivatives to react at the N7 position of guanine moieties in DNA. Simple repetitive probes, cosmids, PACs, and chromosome-specific painting probes were labeled by ULS and used in a series of multicolor fluorescence in situ hybridization experiments on interphase and metaphase cells. It is demonstrated that ULS-labeled probes, in general, perform as well as the more conventional enzymatically labeled probes. The advantage of ULS labeling over enzymatic labeling techniques is that it is a fast and simple procedure, and that the labeling can easily be scaled up for bulk probe synthesis. In addition, with ULS labeling it is possible to label degraded DNA, a situation in which enzymatic labeling is known to perform unsatisfactorily.
A Metric Evaluation of Game Application Software (2005)

In this paper we evaluate the exploitation of object technology as it is used in a test suite of game application software. We use several well-known metrics and apply them to both the game application software and a test suite of language processing tools to form a basis of comparing the two groups. We have developed a metric computation system that uses the g 4 re infrastructure to analyze the C++ programs. We present some results for the two groups of applications and draw some conclusions about the modularity, use of inheritance, and the complexity of methods in these applications. 1.
Alkaloid Biosynthesis: Metabolism and Trafficking (2008)

Alkaloids represent a highly diverse group of compounds that are related only by the occurrence of a nitrogen atom in a heterocyclic ring. Plants are estimated to produce approximately 12,000 different alkaloids, which can be organized into groups according to their carbon skeletal structures. Alkaloid biosynthesis in plants involves many catalytic steps, catalyzed by enzymes that belong to a wide range of protein families. The characterization of novel alkaloid biosynthetic enzymes in terms of structural biochemistry, molecular and cell biology, and biotechnological applications has been the focus of research over the past several years. The application of genomics to the alkaloid field has accelerated the discovery of cDNAs encoding previously elusive biosynthetic enzymes. Other technologies, such as large-scale gene expression analyses and metabolic engineering approaches with transgenic plants, have provided new insights into the regulatory architecture of alkaloid metabolism.