gebhart/patrepeval huggingface dataset:
The ageing lens and cataract: a model of normal and pathological ageing (2011)

Cataract is a visible opacity in the lens substance, which, when located on the visual axis, leads to visual loss. Age-related cataract is a cause of blindness on a global scale involving genetic and environmental influences. With ageing, lens proteins undergo non-enzymatic, post-translational modification and the accumulation of fluorescent chromophores, increasing susceptibility to oxidation and cross-linking and increased light-scatter. Because the human lens grows throughout life, the lens core is exposed for a longer period to such influences and the risk of oxidative damage increases in the fourth decade when a barrier to the transport of glutathione forms around the lens nucleus. Consequently, as the lens ages, its transparency falls and the nucleus becomes more rigid, resisting the change in shape necessary for accommodation. This is the basis of presbyopia. In some individuals, the steady accumulation of chromophores and complex, insoluble crystallin aggregates in the lens nucleus leads to the formation of a brown nuclear cataract. The process is homogeneous and the affected lens fibres retain their gross morphology. Cortical opacities are due to changes in membrane permeability and enzyme function and shear-stress damage to lens fibres with continued accommodative effort. Unlike nuclear cataract, progression is intermittent, stepwise and non-uniform.
Antibody-Catalyzed Degradation of Cocaine (1993)

Immunization with a phosphonate monoester transition-state analog of cocaine provided monoclonal antibodies capable of catalyzing the hydrolysis of the cocaine benzoyl ester group. An assay for the degradation of radiolabeled cocaine identified active enzymes. Benzoyl esterolysis yields ecgonine methyl ester and benzoic acid, fragments devoid of cocaine's stimulant activity. Passive immunization with such an artificial enzyme could provide a treatment for dependence by blunting reinforcement.
Heterologous protein production in the yeastKluyveromyces lactis (2006)

Kluyveromyces lactis is both scientifically and biotechnologically one of the most important non-Saccharomyces yeasts. Its biotechnological significance builds on its history of safe use in the food industry and its well-known ability to produce enzymes like lactase and bovine chymosin on an industrial scale. In this article, we review the various strains, genetic techniques and molecular tools currently available for the use of K. lactis as a host for protein expression. Additionally, we present data illustrating the recent use of proteomics studies to identify cellular bottlenecks that impede heterologous protein expression.
Recombination Drives the Evolution of GC-Content in the Human Genome (2004)

Unraveling the evolutionary forces responsible for variations of neutral substitution patterns among taxa or along genomes is a major issue in the identification of functional sequence features. Mammalian genomes show large-scale regional variations of GC-content (the isochores), but the substitution processes at the origin of this structure are poorly understood. We have analyzed the pattern of neutral substitutions in 14.3 Mb of primate noncoding regions. We show that the GC-content toward which sequences are evolving is strongly correlated (r(2) = 0.61, P </= 2 10(-16)) with the rate of crossovers (notably in females). This demonstrates that recombination drives the evolution of base composition in human (probably via the process of biased gene conversion). The present substitution patterns are very different from what they had been in the past, resulting in a major modification of the isochore structure of our genome. This non-equilibrium situation suggests that changes of recombination rates occur relatively frequently during evolution, possibly as a consequence of karyotype rearrangements. These results have important implications for understanding the spatial and temporal variations of substitution processes in a broad range of sexual organisms, and for detecting the hallmarks of natural selection in DNA sequences.
The primary structure of a plant storage protein: zein (1981)

The protein sequence of a representative of the zeins, the major storage proteins of maize, has been derived from the nucleotide sequence of a zein cDNA clone. This cDNA was sequence both by the Maxam and Gilbert and the M13-dideoxy techniques. The nucleotide sequence encompasses the non-translated 3' terminus of the mRNA, the entire coding sequence specifying both the mature zein protein and a small signal peptide, and a portion of the non-translated 5' region. The deduced amino acid composition and the amino-terminal amino acid sequence closely resemble those derived from chemical analysis of the zein protein fraction. The data presented represent the first complete amino acid sequence of a plant storage protein.
Genetic Targeting Strategies for Adenovirus (2005)

Adenovirus serotype 5 (Ad5) continues to be regarded as a gene delivery vehicle of high utility for a variety of clinical applications. However, targeting of the virus to alternate, non-native receptors has become a mandate for many gene therapy approaches, as inefficient viral transduction of target tissues has proven detrimental to the utility of Ad5. Thus, various targeting strategies have been endeavored to the end of highly specific cellular transduction, including that of genetic manipulation of the viral capsid. Modification of the tropism-determining fiber protein and other capsid locales has allowed vectorologists to develop vectors that are highly superior to the first-generation adenoviruses employed for gene therapy. Herein, the various genetic targeting strategies for Ad5 are reviewed, and the various schemas in which targeted transduction has been achieved with tropism-modified vectors are outlined.
On the Formation and Morphology of Lipid Nanoparticles Containing Ionizable Cationic Lipids and siRNA (2018)

Lipid nanoparticles (LNPs) containing short interfering RNA (LNP-siRNA) and optimized ionizable cationic lipids are now clinically validated systems for silencing disease-causing genes in hepatocytes following intravenous administration. However, the mechanism of formation and certain structural features of LNP-siRNA remain obscure. These systems are formed from lipid mixtures (cationic lipid, distearoylphosphatidylcholine, cholesterol, and PEG-lipid) dissolved in ethanol that is rapidly mixed with siRNA in aqueous buffer at a pH (pH 4) where the ionizable lipid is positively charged. The resulting dispersion is then dialyzed against a normal saline buffer to remove residual ethanol and raise the pH to 7.4 (above the p K<sub>a</sub> of the cationic lipid) to produce the finished LNP-siRNA systems. Here we provide cryogenic transmission electron microscopy (cryo-TEM) and X-ray evidence that the complexes formed between siRNA and ionizable lipid at pH 4 correspond to tightly packed bilayer structures with siRNA sandwiched between closely apposed monolayers. Further, it is shown that ionizable lipid not complexed to siRNA promotes formation of very small vesicular structures at pH 4 that coalesce to form larger LNP structures with amorphous electron dense cores at pH 7.4. A mechanism of formation of LNP-siRNA systems is proposed whereby siRNA is first sandwiched between closely apposed lipid monolayers at pH 4 and subsequently trapped in these structures as the pH is raised to 7.4, whereas ionizable lipid not interacting with siRNA moves from bilayer structure to adopt an amorphous oil phase located in the center of the LNP as the pH is raised. This model is discussed in terms of previous hypotheses and potential relevance to the design of LNP-siRNA systems.
Possible involvement of protein kinases and Smad2 signaling pathways on osteoclast differentiation enhanced by activin A (2001)

Bone tissues reportedly contain considerable amounts of activin A and follistatin, an activin A-binding protein. In the present study, we found that follistatin strongly inhibited osteoclast formation in cocultures of mouse bone marrow cells and primary osteoblasts induced by 1alpha,25 dihydroxyvitamin D(3), prostaglandin E(2), and interleukin-1alpha. Antibody aganist activin A also inhibited the osteoclast formation. Furthermore, activin A synergistically stimulated osteoclast differentiation mediated by receptor activator NF-kappaB ligand (RANKL). RT-PCR analysis revealed that osteoblasts produced not only activin A but also follistatin. Western blot analysis of a panel of phosphorylated proteins revealed that activin A stimulated the phosphorylation of p44/42 mitogen activated protein (MAP) kinase (ERK1/2) and p38 MAP kinase in macrophage colony-stimulating factor-dependent bone marrow macrophages (M-BMMPhis). In addition, phosphorylation of Smad2 was observed in M-BMMPhis stimulated with activin A. These findings indicate that the phosphorylation of p44/42 MAP kinase, p38 MAP kinase, and Smad2 is involved in activin A-enhanced osteoclast differentiation induced by RANKL. Taken together, these results suggest that both activin A and follistatin produced by osteoblasts may play an important role in osteoclast differentiation through MAP kinases and Smad2 signaling pathways.
Prospective comparison of subcutaneous to intravenous administration of bortezomib in patients with multiple myeloma: Pharmacokinetics, efficacy and toxicity (2007)

8046 Bortezomib (Bz) is a novel proteasome inhibitor that is registered for treatment of relapsed or refractory MM as an IV bolus injection. Animal toxicology studies have indicated good local tolerability and an acceptable PK profile of SC injection of Bz supporting together with preliminary clinical data the exploration of this route of administration in humans. We conducted a randomized trial to compare pharmacokinetics/pharmacodynamics (PK/PD), toxicity and efficacy of SC and IV injections of Bz, both at standard dose of 1.3 mg/m 2 twice weekly for 2 wks (day 1–4-8–11), with 1 wk rest, for up to 8 cycles. From 01/06 to 10/06, 24 pts with relapsed/refractory MM were randomized to receive Bz either IV (arm A, n = 12) or SC (arm B, n = 12); Patients received a median number of 5 cycles in both groups. The local tolerance of SC injections was good. Response rates were similar in both groups (CR+VGPR/PR/MR: 3/2/1 in arm A, vs 3/2/2 patients in arm B. Grade 3 / 4 adverse events occurred in 7 cases in arm A, vs 5 in arm B, leading to study discontinuation in 5 and 3 cases, respectively. PK analysis: average plasma Cmax values were lower for SC as compared to IV (15 ng/mL at day 1, and 23 at day 11, vs 130 and 127, p &lt; .001), but overall systemic availability as measured by plasma AUC values were comparable between SC and IV administration for both day 1 &amp; 11 (145 and 388 ng.h/mL, vs 133 and 386, p =.7 &amp; .98, respectively). Average Tmax values were less than 1 hour for both routes. PD analysis (20S proteasome inhibition): average area under the curve for effect (AUE) values were comparable between SC and IV administration both for day 1 &amp; 11 (761 and 1,324 %.h, vs 1,089 and 1,110, p = .29 &amp; .54, respectively), while average Emax values were lower for SC administration (Emax day 1 &amp; day 11 SC, 58 and 56%, vs 72 and 69% IV, p =.003 &amp; .01 respectively). The overall systemic availability of Bz was comparable between SC and IV administration for both day 1 and 11. Similarly, the average AUE results were comparable between SC and IV, while average Emax was lower for SC administration. Response rates were identical in the 2 groups of patients, with similar toxicity profile. Given the good local tolerance of SC injection, this route of administration could be an alternative option to IV injection. [Table: see text]
Characterization of the rat and mouse homologues of the BRCA2 breast cancer susceptibility gene. (1997)

Inherited BRCA2 mutations confer profound susceptibility to human breast and ovarian cancer. The rat and mouse Brca2 homologues share 58% and 59% identity (72% similarity), respectively, with the human BRCA2 protein. The Brca2 proteins also share a potential nuclear localization signal (human codons 3263-3269) and a highly conserved large carboxyl region (77% identity, 86% similarity between human and rodents) that may represent important functional domains. At least six of eight previously described BRC repeats have been highly conserved in rats and mice. Expression studies demonstrate an 11-12 Kb transcript with rodent tissue-specific patterns of expression consistent with human BRCA2. These results will facilitate studies of Brca2 function during normal and neoplastic development.
Recurrent Fusion Oncogenes in Carcinomas (2006)

Chromosome structural aberrations giving rise to fusion oncogenes is one of the most common mechanisms in oncogenesis. Although this type of gene rearrangement has long been recognized as a fundamental pathogenetic mechanism in hematologi-cal malignancies and soft-tissue tumors, it has until recently only rarely been described in the common carcinomas. In this review, the existing information on recurrent fusion oncogenes characterizing carcinomas is summarized, namely, the RET and NTRK1 fusion oncogenes in papillary thyroid carcinoma, PAX8-PPARG in follicular thyroid carcinoma, MECT1-MAML2 in mucoepidermoid carcinoma, the TFE3 and TFEB fusion oncogenes in kidney carcinomas, BRD4-NUT in midline carcinomas, ETV6-NTRK3 in secretory breast carcinomas, and TMPRSS2-ETS fusion oncogenes in prostate carcinomas. As in hematological and soft-tissue malignancies, the most common types of genes involved in fusion oncogenes in carcinomas are transcription factors and tyrosine kinases. With a few exceptions, most fusion oncogenes are tumor type specific in carcinomas, as in other cancers. The mechanisms behind the relative specificity of this type of somatic mutation involve the cellular environment influencing the selection of oncogenic fusions, and the oncogenic fusions in turn driving differentiation programs that may alter the cellular environment. The data summarized on different types of carcinomas characterized by fusion oncogenes indicate that the pathogenetic mechanisms involved in epithelial carcino-genesis may be similar to those known to operate in hematological and soft-tissue malignancies, and further anticipates that many more fusion oncogenes await identification in the most common types of human cancer.
Inhibition of Human Immunodeficiency Virus Type 1 Replication in Primary Macrophages by Using Tat- or CCR5-Specific Small Interfering RNAs Expressed from a Lentivirus Vector (2003)

Although several groups have demonstrated that RNA interference, induced by transfection of small interfering RNA (siRNA) duplexes, can protect cells against a viral challenge in culture, this protection is transient. Here, we describe lentivirus expression vectors that can stably express siRNAs at levels sufficient to block virus replication. We have used these vectors to stably express siRNAs specific for the essential human immunodeficiency virus type 1 (HIV-1) Tat transcription factor or specific for a cellular coreceptor, CCR5, that is required for infection by the majority of primary HIV-1 isolates. These lentivirus vectors are shown to protect cells, including primary macrophages, against HIV-1 infection in culture by inducing selective degradation of their target mRNA species. These data suggest that it should be possible to block the expression of specific viral or cellular genes in vivo by using viral vectors to stably express the appropriate siRNAs.
Protection against Anthrax Toxemia by Hexa- d -Arginine In Vitro and In Vivo (2003)

The anthrax toxin protective antigen precursor is activated by proteolytic cleavage by furin or a furin-like protease. We present here data demonstrating that the small stable furin inhibitor hexa-D-arginine amide delays anthrax toxin-induced toxemia both in cells and in live animals, suggesting that furin inhibition may represent a reasonable avenue for therapeutic intervention in anthrax.
Emergency EEG and continuous EEG monitoring in acute ischemic stroke. (2005)

There is physiologic coupling of EEG morphology, frequencies, and amplitudes with cerebral blood flow. Intraoperative continuous electroencephalographic monitoring (CEEG) is an established modality that has been used for 30 years to detect cerebral ischemia during carotid surgery. These facts have generated interest in applying EEG/CEEG in the intensive care unit to monitor cerebral ischemia. However, its use in acute ischemic stroke (AIS) has been limited, and its value has been questioned in comparison with modern MRI imaging techniques and the clinical neurologic examination. This review presents evidence that EEG/CEEG adds value to early diagnosis, outcome prediction, patient selection for treatment, clinical management, and seizure detection in AIS. Research studies correlating EEG/CEEG and advanced imaging techniques in AIS are encouraged. Improvements in real-time ischemia detection systems are needed for EEG/CEEG to have wider application in AIS.
Is Endothelium the Origin of Endothelial Progenitor Cells? (2010)

Endothelial cells provide the dynamic lining of blood vessels throughout the body and provide many tissue-specific functions, in addition to providing a nonthrombogenic surface for blood cells and conduit for oxygen and nutrient delivery. As might be expected, some endothelial cells are injured or become senescent and are sloughed into the bloodstream, and most circulating endothelial cells display evidence of undergoing apoptosis or necrosis. However, there are rare viable circulating endothelial cells that display properties consistent with those of a progenitor cell for the endothelial lineage. This article reviews historical and current literature to present some evidence that the endothelial lining of blood vessels may serve as a source for rare endothelial colony-forming cells that display clonal proliferative potential, self-renewal, and in vivo vessel forming ability. The article also discusses the current gaps in our knowledge to prove whether the colony-forming cells are in fact derived from vascular endothelium.
Identification of N-Glycosylation in Hepatocellular Carcinoma Patients’ Serum with a Comparative Proteomic Approach (2013)

Our work provides a systematic and quantitative method of glycoproteomics and demonstrates some key changes in clinical HCC serum. These proteomic signatures may help to unveil the underlying mechanisms of hepatocarcinogenesis and may be useful for the exploration of candidate biomarkers.
In Situ Hybridization of Prostate-Specific Antigen mRNA in Human Prostate (1990)

Prostate-specific antigen (PSA) mRNA was detected by in situ hybridization utilizing a 428 base pair [35S]-labelled cDNA probe from the 3' noncoding region of the PSA gene. Thirty six fresh surgical specimens were collected from patients undergoing radical retropubic prostatectomy for carcinoma of the prostate. Quantitative analysis of the levels of PSA mRNA in both the benign and malignant tissues was performed using an IBAS 2000 Image Analysis System. The results of this study demonstrated that there is a significant decrease in the expression of PSA mRNA in the carcinoma tissue when compared to the benign epithelium. The average binding (number of silver grains/1 x 10(4) microns. 2) for 20 specimens of malignant epithelium was 475 +/- 161 and 586 +/- 140 for 16 specimens of benign epithelium (p less than 0.05). Eleven patients had both benign and malignant tissue from the same surgical specimen available for study. From these paired specimens, the PSA mRNA expression was also significantly reduced in the malignant epithelium when compared to the benign epithelium, 445 +/- 162 and 588 +/- 135 respectively (p less than 0.005). The PSA protein was detected using a monoclonal antibody to PSA with an immunohistochemical staining technique. The PSA protein expression paralleled the expression of the PSA mRNA in the majority of the tissue sections. Many of the tumor specimens showed a heterogeneous expression of PSA, whereas all of the benign epithelium had a uniform high level of PSA expression. In conclusion, PSA mRNA and protein are located only within the glandular epithelial tissue, the expression of PSA protein parallels that of the PSA mRNA, and both the PSA protein and PSA mRNA are significantly decreased in the malignant epithelium when compared to benign prostatic epithelium.
Microencapsulation using emulsification/solvent evaporation: an overview of techniques and applications. (1990)

This review describes the microencapsulation of pharmaceuticals using the technique of emulsification-solvent evaporation. Guidelines are given for development of encapsulation processes for drugs with either high or low aqueous solubilities. Methods for microsphere characterization and assessment are detailed. The properties of a range of encapsulating polymers are described with examples of drugs encapsulated. The article concludes by speculating the clinical potential of microsphere-based drug delivery systems.
Huntingtin interacts with cystathionine beta-synthase (1998)

We have screened a rat brain library to identify proteins which interact with the 5'-end of huntingtin (amino acids 1-171), including the polyglutamine tract, in the yeast two-hybrid system. We detected an interaction with cystathionine beta-synthase (CBS) [L-serine hydrolyase (adding homocysteine), EC 4.2.1.22], which was confirmed in vitro using His-tagged CBS expressed in Escherichia coli , which was able to specifically bind both rat and human full-length huntingtin. Neither normal nor expanded polyglutamine repeat alone interacted with CBS in the yeast two-hybrid system and nor did constructs containing SBMA or DRPLA with normal or expanded polyglutamine tracts. CBS therefore appears to bind specifically to huntingtin. CBS deficiency is associated with homocystinuria, which is known to affect various physiological systems, including the central nervous system. Homocysteine, one of the substrates of CBS, is known to accumulate in homocystinuria and is metabolized to homocysteate and homocysteine sulphinate, both known to be powerful excitotoxic amino acids. It has been suggested that Huntington's disease involves the action of excitotoxic amino acids and this interaction with CBS may suggest a mechanism for such excitotoxic damage.
Gene targeting and gene transfer studies of the plaeminogen/plasmin system: implications in thrombosis, hemostasis, neointima formation, and atherosclerosis (1995)

The plasminogen/plasmin or fibrinolytic system with its physiological triggers, tissue-type plasminogen activator, and urokinase-type plasminogen activator has been presumed to participate in normal and pathological processes of the vessel wall such as blood clot dissolution (thrombolysis), hemostasis, aneurysm formation, neovascularization, restenosis, and atherosclerosis. The implied role of the fibrinolytic system in vivo is, however, deduced from correlations between fibrinolytic activity and (patho)physiological phenomena, which does not allow establishing a cause/consequence relationship. Gene targeting and gene transfer technologies allow establishment of the in vivo role of gene products more conclusively. This article reviews briefly the findings of such studies on thrombolysis/thrombosis, hemostasis, neointima formation, atherosclerosis, and associated effects on survival.
Tailigator: Cooperative System for Safety Distance Observance (2016)

A driver's inattention to or disregard for the minimum safety distance creates a hazardous situation in which avoiding a rear-end collision is nearly impossible. In a joint effort to implement safety and decision-making processes at an individual level, we present in this paper a cooperative approach to increase the driver's visual awareness of safe distances. Our Tailigator system garners information through the stereoscopic capturing and processing of images by rear cameras to calculate the distance from the leading to a following vehicle. Visual data related to the safety distance is provided to the rear vehicle in real-time, relying on an asynchronous collaborative process. Results from the system qualitative evaluation are discussed.