gebhart/patrepeval huggingface dataset:
HIV‐1 Egress is Gated Through Late Endosomal Membranes (2003)

HIV-1 buds from the surface of activated T lymphocytes. In macrophages, however, newly formed HIV-1 particles amass in the lumen of an intracellular compartment. Here, we demonstrate by live-cell imaging techniques, by immunocytochemistry and by immuno-electron microscopy that HIV-1 structural proteins, particularly the internal structural protein Gag, accumulate at membranes of the late endocytic compartment in a variety of cell types and not just in monocyte/macrophage-derived cells. Recent biochemical and genetic studies have implicated components of the mammalian vacuolar protein sorting pathway in retroviral budding. Together with those observations, our study suggests that HIV-1 morphogenesis is thoroughly rooted in the endosomal system.
Hypolipidemic treatment of heterozygous familial hypercholesterolemia: a lifelong challenge (2004)

In familial hypercholesterolemia, a defect in low-density lipoprotein receptors causes lifelong two- to threefold elevations in serum low-density lipoprotein-cholesterol levels. This leads to early atherosclerotic changes in infancy. Lifelong hypolipidemic treatment that can be started at a young age is thus greatly needed. Early diagnosis of familial hypercholesterolemia is important, and improved DNA tests for low-density lipoprotein receptor mutations have made it possible to carry out diagnosis at birth. A low saturated-fat, low cholesterol diet can be safely started at 7 months of age. This can be accompanied by dietary stanol esters from 2 years of age. At the age of 10, statin treatment can be safely started. In adults, more aggressive hypolipidemic treatment is required in order to reach the treatment goal for serum low-density lipoprotein-cholesterol levels less than 2.5 mmol/l. This can be achieved by using high doses of statin, or preferably by combining a statin with resin or ezetimibe (Zeita), Merck and Shering-Plough Pharmaceuticals). Once started, treatment of familial hypercholesterolemia is lifelong.
Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels (2002)

Unintended block of HERG K+ channels is a side effect of many common medications and is the most common cause of acquired long QT syndrome associated with increased risk of life-threatening arrhythmias. The molecular mechanism of high-affinity HERG block by structurally diverse compounds has been attributed to pi-stacking and cation-pi interactions of a drug (e.g., cisapride) with specific aromatic amino acid residues (Tyr-652 and Phe-656) in the S6 alpha-helical domain that face the central cavity of the channel. It also has been proposed that strong C-type inactivation of HERG facilitates or is the primary determinant of high-affinity drug binding. The structurally related, but noninactivating eag channel is insensitive to HERG blockers unless inactivation is induced by specific amino acid mutations [Ficker, E., Jarolimek, W. & Brown, A. M. (2001) Mol. Pharmacol. 60, 1343-1348]. Here we examine the relative importance of inactivation vs. positioning of S6 aromatic residues in determining sensitivity of HERG and eag channels to block by cisapride. The repositioning of Tyr-652 or Phe-656 along the S6 alpha-helical domain of HERG reduced sensitivity of channels to block by cisapride. Moreover, independent of inactivation, repositioning of the equivalent aromatic residues in Drosophila eag channels induced sensitivity to block by cisapride. These findings suggest that positioning of S6 aromatic residues relative to the central cavity of the channel, not inactivation per se determines drug block of HERG or eag channels.
Cytokinin/auxin balance in crown gall tumors is regulated by specific loci in the T-DNA (1983)

Insertion of the transposon Tn5 into the T-region of the octopine Ti plasmid of Agrobacterium tumefaciens gives rise to crown gall tumors having altered morphology. Three loci within the T-DNA that control tumor morphology have been detected [Garfinkel, D. J., Simpson, R. B., Ream, L. W., White, F. F., Gordon, M. P. & Nester, E. W. (1981) Cell 27, 143-153]. They influence tumor size (tml), production of roots (tmr), or production of shoots (tms). Cytokinin and auxin levels in such mutant tumors were examined by HPLC/radioimmunoassay and HPLC/fluorescence assay, respectively. Free indoleacetic acid levels (in pmol/g) were: uninfected tobacco stem tissues, 128; wild-type A348 tumors, 295; tml mutant tumors, 307; tmr mutant tumors, 129; and tms mutant tumors, 70. Average trans-ribosylzeatin levels were correspondingly: 0.97, 48, 40, 0.54, and 1,400 pmol/g. trans-Ribosylzeatin/indoleacetic acid ratios were as high as 24 in shoot-producing tumors and as low as 0.003 in root-producing tumors. The evidence strongly suggests that tumor phytohormone levels are determined by genes in the T-DNA.
4-(4,6-Dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium Chloride (DMTMM): A Valuable Alternative to PyBOP for Solid Phase Peptide Synthesis (2000)

The salt formed from 2-chloro-4,6-dimethoxy[1,3,5]triazine and N- methylmorpholine (DMTMM) is an effective coupling agent for solid phase peptide synthesis that can be used as economical alternative to PyBOP. Several oligopeptides were prepared on a Wang type resin using this reagent and the yields and purity of the products were always comparable with those obtained with PyBOP as the coupling agent.
Quantitative observations of flagellar motility of capacitating human spermatozoa (1997)

For technical reasons sperm head movement is assessed in kinematic analysis, while flagellar movement is the determining factor of head movement, not vice versa. It follows then that the development of new kinematic values to describe the movement of capacitating human spermatozoa should include the analysis of their flagellar movement. The aim of this study was to establish quantitative differences between flagellar movement patterns of hyperactivated and non-hyperactivated spermatozoa which could then be used in the evaluation of new centroid-based kinematic values. Spermatozoa were prepared by swim-up from semen into culture medium supplemented with 30 mg/ml human serum albumin. Sperm movement was recorded in 50 microm-deep chambers using a 200 Hz video system. Sperm movement was classified based on flagellar movement, with 24 non-hyperactivated and 26 hyperactivated spermatozoa included in the study. Flagellar analysis was performed using both a semi-automated analysis system (SIAM FLAG; 30 images at 200 Hz) and manual methods (100 Hz). Hyperactivated spermatozoa had significantly larger flagellar beat angles (> or = 87 degrees) and significantly lower flagellar beat frequencies (< or = 29.4 Hz) than non-hyperactivated human spermatozoa. In addition, the flagellar wave amplitude was significantly greater and the bend diameter significantly smaller for hyperactivated spermatozoa in the proximal region of the flagellum (up to 20 microm from the head-midpiece junction). The velocity of the hyperactivated wave was low in this region, although it was significantly slower than the non-hyperactivated wave in all regions of the sperm tail.
Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles (2005)

Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older biokinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.
The role of trace elements in uraemic toxicity (2002)

Although most research on uraemic toxicity has focused on the retention or removal of organic solutes, subtle changes in the concentration of inorganic compounds are also of importance because these compounds may have significant clinical consequences. Potential clinical implications include increased risk of cancer, cardiovascular disease, immune deficiency, anaemia, renal function impairment and bone disease. In uraemic patients, the most important factor affecting trace element concentration is the degree of renal failure and modality of renal replacement therapy. Accumulation of trace elements in haemodialysis patients has resulted from dialysate contaminated with aluminium and strontium. Several trace elements have been implicated in the decline of renal function. These include arsenic, cadmium, copper, germanium, lead and mercury. In uraemic patients, aluminium, cadmium, chromium, lanthanum, strontium and zinc have been shown to accumulate in bone. In addition to substantial evidence linking aluminium to renal osteodystrophy, studies have also implicated cadmium, iron and strontium in bone disease. Studies using a rat model of chronic renal failure have demonstrated an association between lanthanum accumulation and mineralization defects characteristic of osteomalacia. Investigations of arsenic accumulation in animal models have demonstrated that speciation of trace elements potentially may alter toxicities of trace elements accumulated in uraemic patients. Conversely, the presence of uraemic toxins may also alter the uptake and toxicity of certain trace elements. Although research in uraemic patients has focused primarily on total concentrations of trace elements, the evolution of both inorganic and organic species should be considered separately.
Adverse Reactions to Human Serum Albumin (1993)

Controlled studies involving large numbers of patients are not currently available for an accurate assessment of the incidence of adverse effects attributable to HSA administration. Many of the reported reactions appear to be extensions of albumin's pharmacologic activities and would be expected to worsen following large doses of HSA.
Role of Mesalazine in Acute and Long-Term Treatment of Ulcerative Colitis and Its Complications (2002)

Mesalazine represents effective and well-tolerated first-line therapy for mildly to moderately acute disease as well as for the long-term maintenance treatment in the patient with ulcerative colitis.
Audio-based context recognition (2005)

The aim of this paper is to investigate the feasibility of an audio-based context recognition system. Here, context recognition refers to the automatic classification of the context or an environment around a device. A system is developed and compared to the accuracy of human listeners in the same task. Particular emphasis is placed on the computational complexity of the methods, since the application is of particular interest in resource-constrained portable devices. Simplistic low-dimensional feature vectors are evaluated against more standard spectral features. Using discriminative training, competitive recognition accuracies are achieved with very low-order hidden Markov models (1-3 Gaussian components). Slight improvement in recognition accuracy is observed when linear data-driven feature transformations are applied to mel-cepstral features. The recognition rate of the system as a function of the test sequence length appears to converge only after about 30 to 60 s. Some degree of accuracy can be achieved even with less than 1-s test sequence lengths. The average reaction time of the human listeners was 14 s, i.e., somewhat smaller, but of the same order as that of the system. The average recognition accuracy of the system was 58% against 69%, obtained in the listening tests in recognizing between 24 everyday contexts. The accuracies in recognizing six high-level classes were 82% for the system and 88% for the subjects.
The Epidemiology of Panic Attacks, Panic Disorder, and Agoraphobia in the National Comorbidity Survey Replication (2006)

Although the major societal burden of panic is caused by PD and PA-AG, isolated PAs also have high prevalence and meaningful role impairment.
Impact of CPAP on asthmatic patients with obstructive sleep apnoea (2006)

The impact of continuous positive airway pressure (CPAP) treatment on the airway responsiveness of asthmatic subjects with obstructive sleep apnoea (OSA) has scarcely been studied. A prospective study was performed comparing the changes in airway responsiveness and quality of life in stable asthmatic OSA patients, before and 6 weeks after their nocturnal CPAP treatment. A total of 20 subjects (11 males and nine females) participated in the study. With the nocturnal CPAP treatment, the apnoea/hypopnoea index dropped from 48.1±23.6·h -1 to 2.6±2.5·h -1 . There were no significant changes in airway responsiveness after CPAP treatment (provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV 1 ; PC 20 2.5 mg·mL -1 (1.4–4.5)) compared with baseline (PC 20 2.2 mg·mL -1 (1.3–3.5)). There was no significant change in FEV 1 either. However, the asthma quality of life of the subjects improved from 5.0±1.2 at baseline to 5.8±0.9 at the end of the study. In conclusion, nocturnal continuous positive airway pressure treatment did not alter airway responsiveness or forced expiratory volume in one second in subjects with stable mild-to-moderate asthma and newly diagnosed obstructive sleep apnoea. However, nocturnal continuous positive airway pressure treatment did improve asthma quality of life.
Hypoxia promotes a dedifferentiated phenotype in ductal breast carcinoma in situ. (2003)

In cultured neuroblastoma cells, hypoxia induces a dedifferentiated phenotype. We tested whether hypoxia-induced dedifferentiation also occurs in vivo in mammary ductal carcinoma in situ with its well-defined lesions and distinct areas of necrosis. Ductal carcinoma in situ cells surrounding the central necrosis have high hypoxia inducible factor-1alpha protein levels, down-regulated estrogen receptor-alpha, and increased expression of the epithelial breast stem cell marker cytokeratin 19; lose their polarization; and acquire an increased nucleus/cytoplasm ratio, hallmarks of poor architectural and cellular differentiation. The hypoxia-induced changes were confirmed in cultured breast cancer cells. We propose that hypoxia-induced dedifferentiation is a mechanism that promotes tumor progression in breast cancer.
Fluorescent Indicators for Imaging Nitric Oxide Production (1999)

The membrane-permeating indicator DAF-FM DA is transformed by intracellular esterases into the highly water-soluble dye DAF-FM, which traps NO produced by NO synthase (NOS) to yield a highly fluorescent triazole compound in cells (see schematic diagram). Monitoring with a fluorescence microscope should allow direct identification of intracellular production and location of NO.
Cord blood transplantation: state of the art (2009)

firm or refute these concerns. We chose to select for WT1 vaccine treatment only those patients with progressing MDS with excess of blasts, because prevention or delay of overt leukemia could outweigh the disadvantage of inducing cytopenia.
A Bright Bio-Inspired Future (2003)

Biominerals are formed through an intimate association of inorganic materials and organic macromolecules. As
 Douglas
 explains in his Perspective, materials scientists increasingly use these materials as an inspiration for new synthetic materials with superior properties. Model systems can also shed light on the mechanisms of biomineral formation.
 Aizenberg et al.
 show how an array of organic posts can relieve stress and hence aide a phase change from an amorphous film to a single calcite crystal. The posts also serve as conduits for the removal of water an impurities. Similar processes may for example play a role in the formation of sea urchin spines.
Morphogenesis of Escherichia coli (1998)

The shape of Escherichia coli is strikingly simple compared to those of higher eukaryotes. In fact, the end result of E. coli morphogenesis is a cylindrical tube with hemispherical caps. It is argued that physical principles affect biological forms. In this view, genes code for products that contribute to the production of suitable structures for physical factors to act upon. After introduction of a physical model, the discussion is focused on the shape-maintaining (peptidoglycan) layer of E. coli. This is followed by a detailed analysis of the structural relationship of the cellular interior to the cytoplasmic membrane. A basic theme of this review is that the transcriptionally active nucleoid and the cytoplasmic translation machinery form a structural continuity with the growing cellular envelope. An attempt has been made to show how this dynamic relationship during the cell cycle affects cell polarity and how it leads to cell division.
Stable isotope methods for the in vivo measurement of lipogenesis and triglyceride metabolism1,2 (2006)

Synthesis of fatty acids (via de novo lipogenesis) and triglycerides are important factors in fat accumulation and the efficiency of animal production. Recently, new stable isotope methods using heavy water (2H2O) have made possible the safe, and relatively easy, measurement of both of these processes in vivo in animals and humans over prolonged periods. These methods also provide information on the relative contribution of glycolysis and glyceroneogenesis to triglyceride synthesis under different physiological settings. The data suggest that numerous dietary factors, including nutrient composition and caloric content, may affect de novo lipogenesis. Significant differences in de novo lipogenesis have also been seen across species and in different tissues. The rates of triglyceride synthesis have been shown to be affected by diet and to differ significantly between different adipose depots, with metabolically active depots (e.g., visceral fat) having much more rapid triglyceride turnover than subcutaneous depots. Dietary fat and the peroxisome proliferator-activated-gamma agonist rosiglitazone have both been shown to influence triglyceride synthesis rates and to increase glyceroneogenesis. A significant portion of triglyceride synthesis is not related to triglyceride accumulation but rather is secondary to active lipolysis and reesterification. The application of these new techniques to animals other than rodents will undoubtedly enhance our understanding of adipose tissue biology and could lead to new methods for improving animal production.
Use of an Iridium-Catalyzed Redox-Neutral Alcohol-Amine Coupling on Kilogram Scale for the Synthesis of a GlyT1 Inhibitor (2011)

A recent development for the efficient and environmentally friendly synthesis of aliphatic amines is the transition-metal-catalyzed redox-neutral coupling of an alcohol and an amine, generally referred to as a “borrowing hydrogen” reaction. In this work, we describe the first kilogram-scale application of this technology in the synthesis of PF-03463275, a GlyT1 inhibitor developed for the treatment of schizophrenia. Using (Cp*IrCl2)2 the reaction has been optimized to achieve catalyst loadings lower than 0.05 mol % iridium (S/C ≥ 2000) while retaining reasonable reaction times (<24 h). Water and a tertiary amine are essential for high catalytic activity, resulting in dramatically increased reaction rates compared to existing literature protocols. Methods for iridium removal are also described.
Etanercept for severe psoriasis and psoriatic arthritis: observations on combination therapy (2002)

Etanercept appears to be a promising immunomodulatory agent that can be used in combination therapy for the treatment of psoriasis, and a prospective controlled trial may be warranted.
Accumulation of Ammonia in Plants Treated with Bialaphos (1986)

前報の結果から, ビアラホス処理植物体内の遊離アンモニア含量の増加が示唆された. そこで処理植物のアンモニア含量を測定し, さらに殺草効果との関連について検討を行なった. ビアラボス処理による遊離アンモニア含量の増加は, 食用ビエ, メヒシバ, イヌビコおよびムラサキハマスゲで確認され, 処理後24～48時間で無処理の約30倍から100倍に達することがわかった また, アンモニアの蓄積は一過性ではなく持続的であった. 器管の間の比較では, 根よりも茎葉部に, 茎よりも葉により多く認められた. このような顕著なアンモニア蓄積は, 供試した他の除草剤には認められず, ビアラホスに特徴的な作用であった.遊離アンモニア濃度の増加は殺草効果の発現に先立って認められ, その上, 両者に高い相関が認められたので, 殺草効果の主原因はアンモニアの毒性によることが強く示唆された.
Expression Profiling of the Maize Flavonoid Pathway Genes Controlled by Estradiol-Inducible Transcription Factors CRC and P (2000)

To determine the scope of gene expression controlled by the maize transcription factors C1/R and P, which are responsible for activating flavonoid synthesis, we used GeneCalling, an open-ended, gel-based, mRNA-profiling technology, to analyze cell suspension lines of the maize inbred Black Mexican Sweet (BMS) that harbored estradiol-inducible versions of these factors. BMS cells were transformed with a continually expressed estrogen receptor/maize C1 activator domain fusion gene (ER-C1) and either a fusion of C1 and R (CRC), P, or luciferase genes regulated by a promoter containing four repeats of an estrogen receptor binding site. Increasing amounts of luciferase activity, anthocyanins, and flavan-4-ols were detected in the respective cell lines after the addition of estradiol. The expression of both known and novel genes was detected simultaneously in these BMS lines by profiling the mRNA isolated from replicate samples at 0, 6, and 24 hr after estradiol treatment. Numerous cDNA fragments were identified that showed a twofold or greater difference in abundance at 6 and 24 hr than at 0 hr. The cDNA fragments from the known flavonoid genes, except chalcone isomerase (chi1), were induced in the CRC-expressing line after hormone induction, whereas only the chalcone synthase (c2) and flavanone/dihydroflavonol reductase (a1) genes were induced in the P-expressing line, as was expected. Many novel cDNA fragments were also induced or repressed by lines expressing CRC alone, P alone, or both transcription factors in unique temporal patterns. The temporal differences and the evidence of repression indicate a more diverse set of regulatory controls by CRC or P than originally expected. GeneCalling analysis was successful in detecting members of complex metabolic pathways and uncovering novel genes that were either coincidentally regulated or directly involved in such pathways.