gebhart/patrepeval huggingface dataset:
Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy (2008)

Gene profiling studies of patients with chronic lymphocytic leukemia (CLL) has revealed increased expression of Ror1, a cell surface receptor tyrosine kinase. The aim of present study was to analyze gene and protein expression of Ror1 in CLL cells and normal blood leukocytes. Gene expression analysis reverse transcription-polymerase chain reaction of ROR1 revealed that all patients with CLL (n = 100) spontaneously expressed ROR1 mRNA whereas enriched blood B and T cells as well as granulocytes from healthy donors (n = 10) were negative. A strong nonphysiological activation signal (PMA/ionomycin) was required to induce expression in vitro in normal lymphocytes. Major genomic aberrations (mutations or truncation) of ROR1 were not observed. Protein expression was analyzed by Western blot using a panel of polyclonal anti-Ror antibodies as well as flow cytometry. Blood lymphocytes from 18/18 CLL patients, but none of the 10 healthy donors, expressed surface Ror1. The majority of CLL cells exhibited Ror1 surface expression (71% mean; range 36-92%) with a mean fluorescence intensity (MFI) of 20 (range 10-45). The corresponding MFI of CD19 on CLL cells was 26 (range 9-48). There was no difference in the Ror1 protein expression comparing IgVH mutated and unmutated cases as well as progressive and nonprogressive CLL patients. Two different variants of the Ror1 protein, 105 and 130 kDa, were identified. The Ror1 protein expression in patients with CLL but not in normal leukocytes merits further studies of its role in the pathobiology of CLL, which may provide a basis for development of Ror1 directed targeted therapy.
Molecular distinctions between heparan sulphate and heparin. Analysis of sulphation patterns indicates that heparan sulphate and heparin are separate families of N-sulphated polysaccharides (1985)

Heparan sulphate and heparin are chemically related alpha beta-linked glycosaminoglycans composed of alternating sequences of glucosamine and uronic acid. The amino sugars may be N-acetylated or N-sulphated, and the latter substituent is unique to these two polysaccharides. Although there is general agreement that heparan sulphate is usually less sulphated than heparin, reproducible differences in their molecular structure have been difficult to identify. We suggest that this is because most of the analytical data have been obtained with degraded materials that are not necessarily representative of complete polysaccharide chains. In the present study intact heparan sulphates, labelled biosynthetically with [3H]glucosamine and Na2(35)SO4, were isolated from the surface membranes of several types of cells in culture. The polysaccharide structure was analysed by complete HNO2 hydrolysis followed by fractionation of the products by gel filtration and high-voltage electrophoresis. Results showed that in all heparan sulphates there were approximately equal numbers of N-sulpho and N-acetyl substituents, arranged in a similar, predominantly segregated, manner along the polysaccharide chain. O-Sulphate groups were in close proximity to the N-sulphate groups but, unlike the latter, the number of O-sulphate groups could vary considerably in heparan sulphates of different cellular origins ranging from 20 to 75 O-sulphate groups per 100 disaccharide units. Inspection of the published data on heparin showed that the N-sulphate frequency was very high (greater than 80% of the glucosamine residues are N-sulphated) and the concentration of O-sulphate groups exceeded that of the N-sulphate groups. We conclude from these and other observations that heparan sulphate and heparin are separate families of N-sulphated glycosaminoglycans.
Metastasis of Hepatocellular Carcinoma to the Right Colon Manifested by Gastrointestinal Bleeding (1999)

An 82-year-old black woman with a history of hepatocellular carcinoma presented with gastrointestinal bleeding. Barium enema and fibrocolonoscopy revealed a 4-cm polypoid mass at the level of the ascending colon with evidence of active bleeding. Biopsies of the lesion proved it to be metastatic hepatocellular carcinoma. Exploratory laparotomy revealed no further dissemination of the tumor, and the patient underwent an ileocolectomy. The serosal side of the colonic lesion was free from tumor, and there was no peritoneal implantation, direct extension, or lymph node involvement. This case represents an extremely rare presentation of metastatic hepatocellular carcinoma.
The Propagation of Radio Waves over the Surface of the Earth and in the Upper Atmosphere (1936)

Simple formulas and graphs are given which represent the ground-wave field intensity at the surface of the earth as radiated from a short vertical antenna at the surface of the earth. The theory is compared to some experimental results reported by other investigators to determine its range of application. The diffraction formula given is theoretically valid only at the lower frequencies; however, it was shown that sky waves are important both day and night and over land and sea at those distances where diffraction would otherwise cause a marked decrease in the received field intensity. The attenuation formula given for the short distances where diffraction may be nelgected is theoretically valid for any frequency and set of ground constants; experimental data are given which show that the formula may be used even at the ultra-high frequencies.
Two stress sensor proteins for the expression of sigmaE regulon: DegS and RseB (2015)

In E. coli, sigmaE-dependent transcription is controlled by regulated-proteolysis of RseA. RseA, which holds sigmaE as an anti-sigma factor, is sequentially digested by DegS, RseP and cytoplasmic proteases to liberate sigmaE in response to dysfunction in outer-membrane biogenesis. Additionally, the sequential proteolysis is regulated by RseB binding to RseA (Fig. 1A). Direct interaction between RseA and RseB inhibits RseA-cleavage by DegS. Both proteolytic activation of DegS and binding disruption of RseB are thus required to initiate sigmaE-stress response. For the induction of sigmaEstress response, DegS and RseB recognize the states of OMP and LPS for outer-membrane biogenesis. DegS is activated by binding of unfolded OMPs and RseB binding to RseA is antagonized by LPS accumulated in periplasm. In this regard, DegS and RseB are proposed to be stress sensor proteins for sigmaE signal transduction. Interestingly, biogenesis of OMP and LPS appears to cross-talk with each other, indicating that dysfunction of either OMP or LPS can initiate RseA proteolysis. This review aims to briefly introduce two stress sensor proteins, DegS and RseB, which regulate sigmaEdependent transcription.
Astrocytes Produce Dendritic Cell-Attracting Chemokines In Vitro and in Multiple Sclerosis Lesions (2005)

As a result of their close association with the blood-brain barrier, astrocytes play an important role in regulating the homing of different leukocyte subsets to the inflamed central nervous system (CNS). In this study, we investigated whether human astrocytes produce chemokines that promote the migration of myeloid dendritic cells (DCs). By reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, we show that cultured human astrocytes stimulated with interleukin-1beta and tumor necrosis factor produce CCL2, CCL3, CCL4, CCL5, CCL20, and CXCL12 that act on immature DCs, but not CCL19 and CCL21, 2 chemokines specific for mature DCs. Compared with controls, supernatants of cytokine-stimulated astrocytes are more effective in promoting the migration of immature monocyte-derived DCs (iMDDCs). Desensitization of CXCR4 (receptor for CXCL12), CCR1-3-5 (shared receptors for CCL3-4-5), and CCR6 (receptor for CCL20) on iMDDC reduces cell migration toward astrocyte supernatants, indicating that astrocytes release biologically relevant amounts of iMDDC-attracting chemokines. By immunohistochemistry, we show that CXCL12 and, to a lesser extent, CCL20 are expressed by reactive astrocytes in multiple sclerosis lesions. These data lend support to the idea that astrocyte-derived chemokines may contribute to immature DC recruitment to the inflamed CNS.
Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. (1996)

Lovastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (the major regulatory enzyme of the mevalonate pathway of cholesterol synthesis), displays antitumor activity in experimental models. We therefore conducted a Phase I trial to characterize the tolerability of lovastatin administered at progressively higher doses to cancer patients. From January 1992 to July 1994, 88 patients with solid tumors (median age, 57 +/- 14 years) were treated p.o. with 7-day courses of lovastatin given monthly at doses ranging from 2 to 45 mg/kg/day. The inhibitory effects of lovastatin were monitored through serum concentrations of cholesterol and ubiquinone, two end products of the mevalonate pathway. Concentrations of lovastatin and its active metabolites were also determined, by bioassay, in the serum of selected patients. Cyclical treatment with lovastatin markedly inhibited the mevalonate pathway, evidenced by reductions in both cholesterol and ubiquinone concentrations, by up to 43 and 49% of pretreatment values, respectively. The effect was transient, however, and its magnitude appeared to be dose independent. Drug concentrations reached up to 3.9 micrometer and were in the range associated with antiproliferative activity in vitro. Myopathy was the dose-limiting toxicity. Other toxicities included nausea, diarrhea, and fatigue. Treatment with ubiquinone was associated with reversal of lovastatin-induced myopathy, and its prophylactic administration prevented the development of this toxicity in a cohort of 56 patients. One minor response was documented in a patient with recurrent high-grade glioma. Lovastatin given p.o. at a dose of 25 mg/kg daily for 7 consecutive days is well tolerated. The occurrence of myopathy, the dose-limiting toxicity, can be prevented by ubiquinone supplementation. To improve on the transient inhibitory activity of this dosing regimen on the mevalonate pathway, alternative schedules based on uninterrupted administration of lovastatin should also be studied.
Hoes For Optical Storage Systems (1988)

In recent years there has been a resurgent of research activities in the area of computer-generated holograms. The results of these activities have been the development of tools and methodologies for making the computer-generated holograms. The tools for making computer-generated holograms have progressed from the CRT displays, computer plotters and computer printers used in the 60&apos;s and 70&apos;s to more sophisticated systems such as laser scanners and E-beam graphic output devices. Many techniques for encoding the wavefront information into the holograms have been investigated 4. Moreover, the limitations imposed on the performance of the computer-generated holograms by the resolutions of the output systems have also been fully explored. It has also been recognized that computer-generated holograms are more versatile and are more compact than conventional lenses. However, the replacement of lenses by computer-generated holograms has not yet taken place due to difficulties both in material processing and fabrication in achieving high light diffraction efficiency in the holographic optics. It is interesting to note that computer-generated holograms belong to the class of diffractive optical elements. With this point of view, one discovers that computer-generated holograms have already been employed in many practical optical applications. For example, multiple beam gratings generated by computer or other means are used currently in compact disc audio players. More recently, computer-generated holograms are further utilized in compact audio disc players and optical disk drives to replace many of the conventional optical components. In this paper we will discuss a number of different computer-generated holograms which have been used in optical data storage systems. The fabrication process of each of these optical elements are also briefly reviewed.
Genetics of Amyotrophic Lateral Sclerosis (2017)

Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disorder of motor neurons that overlaps clinically with frontotemporal dementia (FTD). Investigations of the 10% of ALS cases that are transmitted as dominant traits have revealed numerous gene mutations and variants that either cause these disorders or influence their clinical phenotype. The evolving understanding of the genetic architecture of ALS has illuminated broad themes in the molecular pathophysiology of both familial and sporadic ALS and FTD. These central themes encompass disturbances of protein homeostasis, alterations in the biology of RNA binding proteins, and defects in cytoskeletal dynamics, as well as numerous downstream pathophysiological events. Together, these findings from ALS genetics provide new insight into therapies that target genetically distinct subsets of ALS and FTD.
Genetics of Human Taste Perception (2004)

Genetic approaches are rapidly yielding new information about our sense of taste. This information comes from both molecular studies of genes encoding taste receptors and other taste-signaling components, and from studies of inherited variation in taste abilities. Our understanding of bitter taste has advanced by combined information from discovery and study of the TAS2R family of taste receptor genes, hand in hand with genetic linkage and positional cloning studies, notably on the ability to taste phenylthiocarbamide (PTC). Sweet and umami tastes, mediated by TAS1R receptors, are becoming well-characterized at the molecular genetic level, and these taste classes are now targets for linkage, positional cloning, and genetic association strategies. Salty and sour tastes are still poorly characterized in genetic terms, and represent opportunities for the future.
Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study. (1999)

The highest SMRs in the diabetic cohort were for diabetes and liver cirrhosis. The mortality risk for cardiovascular diseases, although significantly higher than expected, was much lower in Italian type 2 diabetic patients than that reported for American patients. The evidence of an early effect on mortality suggests that prevention, early diagnosis, and treatment should be improved.
5 Empirischer Vergleich der Wörterbuchartikel und Formulierung von Vorschlägen für ausgewählte Phraseme (1998)

5 Empirischer Vergleich der Wörterbuchartikel und Formulierung von Vorschlägen für ausgewählte Phraseme was published in Zur Konzeption eines phraseologischen Wörterbuchs für den Fremdsprachler on page 95.
Chronotherapeutics (light and wake therapy) in affective disorders (2005)

The Committee on Chronotherapeutics, delegated by the International Society for Affective Disorders (ISAD), makes the following recommendations after reviewing the evidence as of November 2004. (1) Wake therapy is the most rapid antidepressant available today: approximately 60% of patients, independent of diagnostic subtype, respond with marked improvement within hours. Treatment can be a single or repeated sleep deprivation, total (all night) or partial (second half of the night). Relapse can be prevented by daily light therapy, concomitant administration of SSRIs, lithium (for bipolar patients), or a short phase advance of sleep over 3 days following a single night of wake therapy. Combinations of these interventions show great promise. (2) Light therapy is effective for major depression--not only for the seasonal subtype. As an adjuvant to conventional antidepressants in unipolar patients, or lithium in bipolar patients, morning light hastens and potentiates the antidepressant response. Light therapy shows benefit even for patients with chronic depression of 2 years or more, outperforming their weak response to drugs. This method provides a viable alternative for patients who refuse, resist or cannot tolerate medication, or for whom drugs may be contraindicated, as in antepartum depression. (3) Given the urgent need for new strategies to treat patients with residual depressive symptoms, clinical trials of wake therapy and/or adjuvant light therapy, coupled with follow-up studies of long-term recurrence, are a high priority.
Synthetic-lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae (1993)

Abplp is a yeast cortical actin-binding protein that contains an SH3 domain similar to those found in signal transduction proteins that function at the membrane/cytoskeleton interface. Although no detectable phenotypes are associated with a disruption allele of ABP1, mutations that create a requirement for this protein have now been isolated in the previously identified gene SAC6 and in two new genes, SLA1 and SLA2. The SAC6 gene encodes yeast fimbrin, an actin filament-bundling protein. Null mutations in SLA1 and SLA2 cause temperature-sensitive growth defects. Sla1p contains three SH3 domains and is essential for the proper formation of the cortical actin cytoskeleton. The COOH terminus of Sla2p contains a 200 amino acid region with homology to the COOH terminus of talin, a membrane cytoskeletal protein which is a component of fibroblast focal adhesions. Sla2p is required for cellular morphogenesis and polarization of the cortical cytoskeleton. In addition, synthetic-lethal interactions were observed for double-mutants containing null alleles of SLA2 and SAC6. In total, the mutant phenotypes, sequences, and genetic interactions indicate that we have identified novel proteins that cooperate to control the dynamic cytoskeletal rearrangements that are required for the development of cell polarity in budding yeast.
Ecologically safe sugar-based gemini surfactants (2006)

Gemini surfactants have appeared in the early 1990s as a new type of surfactants with two polar heads and two alkyl tails linked by an spacer. These structural feature give to these type of surfactants unprecedented and better interfacial properties in comparison with their monomeric counterparts. Alkyl glycosides are monomeric non-ionic surfactants prepared in industrial scale from fatty alcohols and carbohydrates. They are gradually replacing the non-ionic surfactants derived from petrochemical materials. The interesting properties of gemini surfactants prompted us ten years ago to design and synthesize gemini surfactants from alkyl glucoside. Butyl, octyl, dodecyl and tetradecyl glucosides were prepared and linked through O-6 or O-2 via succinyl, glutaryl and terephthloyl spacers. The effect of the position of the linkage, the anomeric configuration of the glucoside, the spacer functionality and the spacer type (rigid or flexible) on the interfacial properties were analized. The physico-chemical parameters of these gemini surfactants were compared with those of their monomeric conterparts. Synergist effects were studied. Molecular modelling and inverse micelle formation are summarized.
Formulations of Sugars with Amino Acids or Mannitol–Influence of Concentration Ratio on the Properties of the Freeze-Concentrate and the Lyophilizate (1998)

Formulations consisting of either sucrose or trehalose with glycine, lysine-HCl, or mannitol were studied to determine how the ratio of the excipients affects the design of the lyophilization program and the properties of the final cake. Glass transitions (Tg', Tg), crystallization temperatures, and eutectic melting temperatures were measured by differential scanning calorimetry, the physical state of the excipients was determined by x-ray powder diffraction, and residual moisture was measured by Karl Fischer titration. The addition of increasing amounts of glycine, lysine-HCl, or mannitol to a sucrose solution caused a progressive depression of the Tg', an effect that was more pronounced with the amino acids. In equivalent ratios with sucrose, the two amino acids induced a comparable Tg' shift due to their low Tg' values. For lysine-HCl, two apparent Tg' with midpoint temperatures of -69 and -56 degrees C were measured. For mannitol, the Tg' depression was unexpected because mannitol exhibits a higher Tg' than that of sucrose. During lyophilization, the ratio of the amorphous amino acids or mannitol to the sugar determined whether crystallization could be induced by an annealing step performed after freezing. Crystallization could be verified by a shift of the formerly depressed Tg' back to the value of the sugar and by the detection of the eutectic melting peak of the crystallized compound. The crystallized excipients served as excellent bulking agents. In the freeze-dried cake, amorphous glycine and even more amorphous mannitol lowered the Tg value. If the cake was stored above Tg, subsequent crystallization of mannitol occurred. The results emphasize that the qualitative and quantitative composition of a formulation has profound implications on the design of a lyophilization program and on the characteristics of the freeze-dried cake.
Seed particle-enabled acoustic trapping of bacteria and nanoparticles in continuous flow systems (2012)

Acoustic trapping of sub-micron particles can allow enrichment and purification of small-sized and low-abundance microorganisms. In this paper, we investigate the dependency of the ability to capture sub-micron particles on the particle concentration. Based on the findings, it is demonstrated that seed particles can be introduced to acoustic trapping, to enable capture of low-abundance sub-micron particles. Without using seed particles, continuous enrichment of 490 nm polystyrene particles is demonstrated in a rectangular capillary with a locally generated acoustic field at high particle concentrations, i.e. above 1% wt. Trapping of sub-micron particles at significantly lower concentrations was subsequently accomplished by seeding 10-12 micrometer-sized particles in the acoustic trap prior to the sub-micron particle capture. Furthermore, the new seeded-particle-aided acoustic trapping technique was employed for the continuous enrichment of bacteria (E. coli) with a capture efficiency of 95%. Finally, seed particle assisted acoustic trapping and enrichment is demonstrated for polymer-based particles down to 110 nm in diameter.
Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages (2000)

Macrophages infected with HIV-1 produce high levels of M-CSF and macrophage-inflammatory protein-1alpha (MIP-1alpha). M-CSF facilitates the growth and differentiation of macrophages, while the chemotactic properties of MIP-1alpha attract both T lymphocytes and macrophages to the site of HIV infection. Studies described in this work indicate M-CSF may function in an autocrine/paracrine manner to sustain HIV replication, and data suggest possible therapeutic strategies for decreasing viral load following HIV infection. We show that macrophage infection with measles virus or respiratory syncytial virus, in contrast to HIV-1, results in production of MIP-1alpha, but not M-CSF. Thus, M-CSF appears to be specifically produced upon infection of macrophages with HIV-1. Furthermore, addition of M-CSF antagonists to HIV-1-infected macrophages, including anti-M-CSF monoclonal or polyclonal Abs or soluble M-CSF receptors, dramatically inhibited HIV-1 replication and reduced production of MIP-1alpha. Our results suggest that biologic antagonists for M-CSF may represent novel strategies for inhibiting the spread of HIV-1 by 1) blocking virus replication in macrophages, 2) reducing recruitment of HIV-susceptible T cells and macrophages by MIP-1alpha, and 3) preventing the establishment and maintenance of infected macrophages as a reservoir for HIV.