gebhart/patrepeval huggingface dataset:
Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in improving contralateral parkinsonism (2006)

Deep brain stimulation (DBS) has an increasing role in the treatment of idiopathic Parkinson's disease. Although, the subthalamic nucleus (STN) is the commonly chosen target, a number of groups have reported that the most effective contact lies dorsal/dorsomedial to the STN (region of the pallidofugal fibres and the rostral zona incerta) or at the junction between the dorsal border of the STN and the latter. We analysed our outcome data from Parkinson's disease patients treated with DBS between April 2002 and June 2004. During this period we moved our target from the STN to the region dorsomedial/medial to it and subsequently targeted the caudal part of the zona incerta nucleus (cZI). We present a comparison of the motor outcomes between these three groups of patients with optimal contacts within the STN (group 1), dorsomedial/medial to the STN (group 2) and in the cZI nucleus (group 3). Thirty-five patients with Parkinson's disease underwent MRI directed implantation of 64 DBS leads into the STN (17), dorsomedial/medial to STN (20) and cZI (27). The primary outcome measure was the contralateral Unified Parkinson's Disease Rating Scale (UPDRS) motor score (off medication/off stimulation versus off medication/on stimulation) measured at follow-up (median time 6 months). The secondary outcome measures were the UPDRS III subscores of tremor, bradykinesia and rigidity. Dyskinesia score, L-dopa medication reduction and stimulation parameters were also recorded. The mean adjusted contralateral UPDRS III score with cZI stimulation was 3.1 (76% reduction) compared to 4.9 (61% reduction) in group 2 and 5.7 (55% reduction) in the STN (P-value for trend <0.001). There was a 93% improvement in tremor with cZI stimulation versus 86% in group 2 versus 61% in group 1 (P-value = 0.01). Adjusted 'off-on' rigidity scores were 1.0 for the cZI group (76% reduction), 2.0 for group 2 (52% reduction) and 2.1 for group 1 (50% reduction) (P-value for trend = 0.002). Bradykinesia was more markedly improved in the cZI group (65%) compared to group 2 (56%) or STN group (59%) (P-value for trend = 0.17). There were no statistically significant differences in the dyskinesia scores, L-dopa medication reduction and stimulation parameters between the three groups. Stimulation related complications were seen in some group 2 patients. High frequency stimulation of the cZI results in greater improvement in contralateral motor scores in Parkinson's disease patients than stimulation of the STN. We discuss the implications of this finding and the potential role played by the ZI in Parkinson's disease.
Isolation of Multipotent Neural Crest‐Derived Stem Cells from the Adult Mouse Cornea (2006)

We report the presence of neural crest-derived corneal precursors (COPs) that initiate spheres by clonal expansion from a single cell. COPs expressed the stem cell markers nestin, Notch1, Musashi-1, and ABCG2 and showed the side population cell phenotype. COPs were multipotent with the ability to differentiate into adipocytes, chondrocytes, as well as neural cells, as shown by the expression of beta-III-tubulin, glial fibrillary acidic protein, and neurofilament-M. COP spheres prepared from E/nestin-enhanced green fluorescent protein (EGFP) mice showed induction of EGFP expression that was not originally observed in the cornea, indicating activation of the neural-specific nestin second intronic enhancer in culture. COPs were Sca-1(+), CD34(+), CD45(-), and c-kit(-). Numerous GFP(+) cells were observed in the corneas of mice transplanted with whole bone marrow of transgenic mice ubiquitously expressing GFP; however, no GFP(+) COP spheres were initiated from these mice. On the other hand, COP spheres from transgenic mice encoding P0-Cre/Floxed-EGFP as well as Wnt1-Cre/Floxed-EGFP were GFP(+), indicating the neural crest origin of COPs, which was confirmed by the expression of the embryonic neural crest markers Twist, Snail, Slug, and Sox9. Taken together, these data indicate the existence of neural crest-derived, multipotent stem cells in the adult cornea.
Complete analysis of the presenilin 1 gene in early onset Alzheimerʼs disease (1996)

The presenilin 1 gene has recently been identified as the locus on chromosome 14 which is responsible for a large proportion of early onset, autosomal dominantly inherited Alzheimer's disease (AD). We have elucidated the intron/exon structure of the gene and designed intronic primers to enable direct sequencing of the entire coding region (10 exons) of the presenilin gene in a large number of families. This strategy has enabled us to find a further two novel mutations in the gene. We discuss the distribution of mutations and the proportions of autosomal dominant AD with a mean age of onset below 60 years caused by mutations in this gene.
The High Mobility Group A1 Gene: Transforming Inflammatory Signals into Cancer? (2010)

High mobility group A1 (HMGA1) is highly expressed during embryogenesis and in poorly differentiated cancers, and high levels portend a poor prognosis in some tumors. HMGA1 induces oncogenic transformation in cultured cells and causes aggressive cancers in transgenic mice, whereas blocking it interferes with transformation in experimental models. These findings suggest a pivotal role for HMGA1 in cancer. This review focuses on two recently described HMGA1 transcriptional targets that mediate inflammatory signals and drive malignant transformation because they could serve as biomarkers or therapeutic targets. Further elucidation of HMGA1 function in transformation promises to have a major impact on our war on cancer.
A spatial interface for audio and music production (2006)

In an effort to find a better suited interface for musical performance, a novel approach has been discovered and developed. At the heart of this approach is the concept of physical interaction with sound in space, where sound processing occurs at various 3-D locations and sending sound signals from one area to another is based on physical models of sound propagation. The control is based on a gestural vocabulary that is familiar to users, involving natural spatial interaction such as translating, rotating, and pointing in 3-D. This research presents a framework to deal with realtime control of 3-D audio, and describes how to construct audio scenes to accomplish various musical tasks. The generality and effectiveness of this approach has enabled us to re-implement several conventional applications, with the benefit of a substantially more powerful interface, and has further led to the conceptualization of several novel applications. 1.
Streptonigrin. 1. Structure-activity relationships among simple bicyclic analogs. Rate dependence of DNA degradation on quinone reduction potential (1986)

A series of simple aza and diaza bicyclic quinones related to the AB ring system of streptonigrin (1) have been synthesized and tested in vitro for their ability to degrade DNA under conditions similar to those used with the parent drug. The results obtained from a study of 22 quinones indicate that there is a quantitative linear relationship between their reduction potentials and the rate at which they degrade DNA under identical conditions in vitro. Almost all of the synthetic substances were superior to 1 in their DNA-degrading ability.
Channel Characterization of Indoor Wireless Personal Area Networks (2006)

The wireless channel for nomadic diversity-based wireless networks operating at 1.9 GHz is characterized. Using a 1 times 2 wideband measurement chain, four typical indoor office and industrial environments have been investigated: a corridor, an office room, a laboratory room and a large industrial hall. The measurement equipment is constituted by an 80-MHz transmitter. At the receiver, two omnidirectional antennas are connected to a wideband channel sounder through a switch, in order to measure an estimate of the instantaneous vector channel. Special attention is given to the experimental procedure itself, so as to take into account the specificity of nomadic systems (as opposed to usual mobile systems). The measurement analysis reveals that the shadowing, Rician K-factor and delay-spread are lognormally distributed. A path-loss model is derived, and cross-correlations between K-factor, delay-spread and shadowing are analyzed. The channel correlations at the user terminal or at the access point are also derived, and related to the individual channel characteristics
Doxorubicin, mitomycin-C, and 5-fluorouracil (DMF) in the treatment of metastatic hormonal refractory adenocarcinoma of the prostate, with a note on the staging of metastatic prostate cancer. (1983)

Sixty-two patients with metastatic hormonal refractory adenocarcinoma of the prostate received a combination of doxorubicin, mitomycin-C, and 5-fluorouracil (DMF). Thirty (48%) of the patients achieved an objective response. Response criteria excluded disease "stabilization" as a manifestation of response. Four clinical prognostic categories were identified: osseous I (OI) had metastatic axial skeletal involvement (23 patients); osseous II (OII) had axial and extremity skeletaL involvement (18 patients); visceral I (VI) had pulmonary metastasis (9 patients); and visceral II (VII) had pulmonary metastasis and involvement of other viscera (12 patients). The 20 responding patients survived a median of 47.5 weeks, whereas the 32 nonresponding patients survived a median of 23.8 weeks (n = 0.002). Response rates were highest among patients with OI (52%) and VI (88%) disease; response rates were lower amont patients with OII (33%) and VII (33%) disease. Responding patients in each clinical category survived longer than nonresponding patients except for those patients with VII disease. The median duration of response for patients with OI disease was 11 months, for OII 9.5 months, for VI patients it was 6.5 months, and VII patients it was 5 months. DMF is an effective treatment of metastatic hormonal refractory prostate cancer, resulting in consistent objective responses. The staging system employed identifies four clinical categories of metastatic prostate cancer and allows for accurate comparison of diet and stratification of study populations.
Synthesis of Tailor‐Made Glycoconjugates Showing AT III‐Mediated Inhibition of Blood Coagulation Factors Xa and Thrombin (1996)

A sufficiently long spacer between the antithrombin- and thrombin-binding domains (ABD and TBD, respectively) is necessary to impart antithrombin activity to a synthetic glycoconjugate (shown schematically below). The spacer need not consist of multiple sugar units as in heparin; a simple chain about 50 atoms in length suffices. In addition, varying the charge density of the TBD affects the inhibitor activity, and symmetric glycoconjugates (TBD = ABD) also display high antithrombin activities.
Macaque ganglion cell responses to stimuli that elicit hyperacuity in man: detection of small displacements (1993)

We measured responses of macaque ganglion cells as a function of contrast in a simple hyperacuity task, detection of displacement of an achromatic edge. Responses of ganglion cells of the magnocellular (MC) pathway were much more vigorous than those of cells of the parvocellular (PC) pathway. From the variability in the number of impulses in the response as compared with the distribution of impulses in maintained activity, it was possible to generate receiver operating characteristics for cells of the two pathways, and to predict individual cells' capability to detect a displacement with 75% probability. On comparing cell sensitivities to human psychophysical thresholds (75% probability of correct identification of displacement direction) at an equivalent retinal eccentricity (approximately 6 degrees), we found that one or two additional impulses in two MC pathway cells would suffice to support an ideal detector underlying psychophysical performance, at all contrast levels. Many more PC pathway cells would be required, especially at low contrasts. The much higher signal-to-noise ratio in the MC pathway relative to the PC pathway indicates that the MC pathway is likely to support this and other hyperacuity tasks.
Effect of omega 3 and omega 6 fatty acids on transformation of cultured cells by irradiation and transfection. (1992)

Mouse embryo fibroblasts (C3H 10T1/2) were exposed to 4 Gy of gamma-rays. The cells yielded 5-8 transformed foci per 10(4) surviving cells. Addition of 100 microM of either eicosapentaenoate or docosahexaenoate to the tissue culture medium reduced the number of transformed foci to 0-1.4. C3H 10T1/2 and NIH 3T3 cells were transfected with plasmid T24 containing the Harvey ras oncogene. C3H 10T1/2 cells yielded 0.85-1.1 foci/ng DNA, while NIH 3T3 cells yielded 0.12-0.14 foci/ng DNA. Foci formation was suppressed 65% in C3H 10T1/2 cells and 93% in NIH 3T3 cells when 100 microM eicosapentaenoate was present in the culture medium. Docosahexaenoate had a similar but somewhat weaker effect. Addition of arachidonate to the medium had little or no effect. Cells grown in the presence of added eicosapentaenoate or docosahexaenoate produced much less prostaglandin E when challenged with calcium ionophore A23187. This is a reflection of changes in arachidonate production or utilization that occur during transformation which are suppressed by the added omega 3 fatty acids. Addition of eicosapentaenoate or docosahexaenoate to the culture medium resulted in extensive remodeling of the molecular species of the four major phospholipid classes that were examined. In its simplest form, omega 3-fatty acid-containing species substantially replaced omega 6-fatty acid-containing species. However, many more subtle changes occurred, and the different phospholipids responded differently to different polyunsaturated fatty acids. A feature of C3H 10T1/2 cells was their preferential accumulation of molecular species of 22-carbon fatty acids such as docosapentaenoate (22:5 omega 3) and docosatetraenoate (22:4 omega 6) in preference to eicosapentaenoate (20:5 omega 3) and eicosapentaenoate (arachidonate, 20:4 omega 6). It is proposed that the protective effect of eicosapentaenoate and docosahexaenoate arises out of the changes in the composition of the fatty acids that are released from one or more phospholipids by the action of phospholipases. The changes consist of a reduced release of arachidonate, the normal substrate of cyclooxygenase and lipoxygenases, and a greatly increased release of eicosapentaenoate and docosahexaenoate, which inhibit one or more of these enzymes, or form oxygenated products which are not as active as the arachidonate-derived products. Other mechanisms are also considered.
Histidine-Lysine Peptides as Carriers of Nucleic Acids (2007)

With their biodegradability and diversity of permutations, peptides have significant potential as carriers of nucleic acids. This review will focus on the sequence and branching patterns of peptide carriers composed primarily of histidines and lysines. While lysines within peptides are important for binding to the negatively charged phosphates, histidines are critical for endosomal lysis enabling nucleic acids to reach the cytosol. Histidine-lysine (HK) polymers by either covalent or ionic bonds with liposomes augment transfection compared to liposome carriers alone. More recently, we have examined peptides as sole carriers of nucleic acids because of their intrinsic advantages compared to the bipartite HK/liposome carriers. With a protocol change and addition of a histidine-rich tail, HK peptides as sole carriers were more effective than liposomes alone in several cell lines. While four-branched polymers with a primary repeating sequence pattern of -HHK- were more effective as carriers of plasmids, eight-branched polymers with a sequence pattern of -HHHK- were more effective as carriers of siRNA. Compared to polyethylenimine, HK carriers of siRNA and plasmids had reduced toxicity. When injected intravenously, HK polymers in complex with plasmids encoding antiangiogenic proteins significantly decreased tumor growth. Furthermore, modification of HK polymers with polyethylene glycol and vascular-specific ligands increased specificity of the polyplex to the tumor by more than 40-fold. Together with further development and insight on the structure of HK polyplexes, HK peptides may prove to be useful as carriers of different forms of nucleic acids both in vitro and in vivo.
The p110δ Isoform of Phosphoinositide 3-Kinase Controls Clonal Expansion and Differentiation of Th Cells (2006)

The role of PI3K in T cell activation and costimulation has been controversial. We previously reported that a kinase-inactivating mutation (D910A) in the p110delta isoform of PI3K results in normal T cell development, but impaired TCR-stimulated cell proliferation in vitro. This proliferative defect can be overcome by providing CD28 costimulation, which raises the question as to whether p110delta activity plays a role in T cell activation in vivo, which occurs primarily in the context of costimulation. In this study, we show that the PI3K signaling pathway in CD28-costimulated p110delta D910A/D910A T cells is impaired, but that ERK phosphorylation and NF-kappaB nuclear translocation are unaffected. Under in vitro conditions of physiological Ag presentation and costimulation, p110delta D910A/D910A T cells showed normal survival, but underwent fewer divisions. Differentiation along the Th1 and Th2 lineages was impaired in p110delta D910A/D910A T cells and could not be rescued by exogenous cytokines in vitro. Adoptive transfer and immunization experiments in mice revealed that clonal expansion and differentiation in response to Ag and physiological costimulation were also compromised. Thus, p110delta contributes significantly to Th cell expansion and differentiation in vitro and in vivo, also in the context of CD28 costimulation.
ATAXIA WITH OPHTHALMOPLEGIA OR SENSORY NEUROPATHY IS FREQUENTLY CAUSED BY POLG MUTATIONS (2009)

![Graphic][1]</img> Progress in molecular genetics unraveled the genetic basis of many subtypes of hereditary ataxias. Dominantly inherited forms are most frequently caused by CAG repeat expansions in the SCA1, SCA2, SCA3, SCA6, and SCA7 genes, whereas intronic GAA repeat expansions in the FRDA gene lead to Friedreich ataxia, the most common autosomal recessive ataxia in the Western world.1 Patients with ataxia who are negative for these mutations remain a major diagnostic challenge since genetic heterogeneity of ataxias is immense and includes a large number of extremely rare disorders.2 Phenotypic characteristics indicating the responsible gene are highly warranted to guide cost-intensive and time-intensive genetic screening. Patients with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) have been reported to carry mutations in the gene coding for DNA polymerase gamma ( POLG ).3–5 To analyze the indicative value of the SANDO phenotype for genetic diagnostics, we screened a cohort of ataxia patients with either external ophthalmoplegia or sensory neuropathy for POLG mutations. ### Methods. Twenty-six patients from 23 nonconsanguineous families with cerebellar ataxia plus sensory neuropathy or external ophthalmoplegia were included in this study. The whole coding region including intron-exon boundaries of the POLG gene was screened by direct sequencing. Primer sequences are noted in table e-1 on the Neurology ® Web site at www.neurology.org. Sensory neuropathy was clinically diagnosed in patients with reduced vibration sense, hyporeflexia at least of lower … [1]: /embed/inline-graphic-1.gif
Identification of a new brain-specific transcription factor, NURR1. (1992)

We have identified and cloned a novel member of the nuclear receptor superfamily. The cDNA was isolated from a mouse brain cDNA library and encodes a protein 598 amino acids in length with a predicted mol wt of 66 kilodaltons. The amino acid sequence of the protein is closely related to an additional family member and immediate early gene product, Nur77, and the novel factor is referred to as Nurr1 (Nur-related factor 1). The relationship between Nurr1 and Nur77 suggests that these proteins constitute an additional subfamily within the nuclear receptor superfamily. Like Nur77, the expression of Nurr1 is induced by membrane depolarization of PC12 cells. However, while Nur77 shows an early transcriptional response to nerve growth factor stimulation, the failure of Nurr1 to respond to this agent suggests a differential selectivity of the two proteins in terms of their transcriptional responses to specific stimuli. Finally, both proteins are differentially expressed during development and in tissues of the adult mouse. Unlike Nur77, Nurr1 appears to be predominantly located in brain tissue, suggesting a primary role for this putative transcription factor in regulation of gene expression in the central nervous system.
Lingual and gastric lipases. (1992)

The 1973 discovery of lingual lipase, which is secreted by lingual serous glands and hydrolyzes medium- and long-chain triglycerides in the stomach, has renewed interest in the gastric phase of fat digestion. In humans, lipase is present in the serous (von Ebner) glands of the tongue, where it is localized in zymogen granules. In the stomach, the highest lipase activity is in the body. By immunocytochemistry, gastric lipase is confined to the chief cells of the fundic mucosa and is colocalized with pepsin. Human lipase purified from lingual serous glands or gastric juice has a MW of 45k to 51K but tends to aggregate (MW 270-300K and 500K) and is highly hydrophobic. Secretion of gastric lipase appears to be stimulated by at least two receptor mechanisms. It has been suggested that the products of gastric lipolysis maintain the sterility of the gastrointestinal tract. These enzymes are essential for the digestion of milk fat in the newborn because, contrary to other digestive lipases (pancreatic or milk digestive lipase), lingual and gastric lipases can penetrate into the milk fat globule and initiate the digestive process. Lingual and gastric lipase activity has been found in subjects with cystic fibrosis and appears to continue in the upper small intestine in these patients, perhaps replacing some of the missing pancreatic lipase. It is possible that lingual and gastric lipase supplements would be more effective in preventing steatorrhea in these patients than are the pancreatic enzyme supplements now given. The same therapeutic utility might be obtained in patients with alcoholic pancreatic insufficiency.