Miracle-dz/UniFAR-FTUs huggingface dataset:
Mirror to America: The Autobiography of John Hope Franklin

John Hope Franklin lived through America's defining twentieth century transformation, the dismantling of legally protected racial segregation. A renowned scholar, he has explored that formation in its myriad aspects, notably in his 3.5 million bestseller, "From Slavery to Freedom". And he experienced it first hand. Born in 1915, he was evicted from whites-only train cars confined to segregated schools, threatened - once with lynching - and consistently faced with racism's denigration of his humanity. And yet he managed to receive a Ph.D. from Harvard; become first black historian to assume a full professorship at a white institution; reshape the way African American history is understood and taught; and personally challenge the racism he chronicled. From his effort in 1934 to force President Franklin Roosevelt to respond to the Cordie Cheek lynching, to his 1997 appointment to head President Clinton's Initiative on Race, Franklin, with determination and dignity, has influenced the America's racial conscience. Franklin's life long fight for civil rights earned him the Presidential Medal of Freedom, America's highest civilian honour. Intimate, at times revelatory, "Mirror to America" chronicles Franklin's life, this America's racial transformation, and the extent to which the problem of America remains the problem of colour.
Escherichia coli K-12 tolZ mutants tolerant to colicins E2, E3, D, Ia, and Ib: defect in generation of the electrochemical proton gradient

Spontaneous Escherichia coli K-12 mutants tolerant to colicin E3 were isolated, and on the basis of their tolerance patterns to 19 kinds of colicins, a new phenotypic class of tolZ mutants was found. The tolZ gene was located between min 77 and 78 on the E. coli K-12 genetic map. The tolZ mutants were tolerant to colicins E2, E3, D, Ia, and Ib, and showed an increased sensitivity to ampicillin, neomycin, and EDTA, but not to deoxycholate; they were able to grow on glucose minimal medium, but not on nonfermentable carbon sources (succinate, acetate, pyruvate, lactate, malate, etc.). The pleiotropic phenotype of the tolZ mutant was due to a single mutation. Both respiration and membrane ATPase activity of the tolZ mutant were normal. The tolZ mutant had a defect in the uptake of proline, glutamine, thiomethyl-beta-D-galactoside, and triphenylmethylphosphonium ion; these uptake systems are driven by an electrochemical proton gradient (delta-mu H+) or a membrane potential (delta psi). In contrast, the uptake of methionine and alpha-methyl-D-glucoside, which is not dependent on delta-mu H+ and delta psi, was normal in the tolZ mutant. Glucose 6-phosphate uptake at pH 5.5, which is driven by a transmembrane pH gradient, in the tolZ mutant was similar to the parent level. These results indicate that the tolZ mutant has a defect in the generation of delta-mu H+ and delta psi.
New perspectives on keratoconus as revealed by corneal confocal microscopy

Confocal microscopy (CM) of keratoconus is reviewed. In the Manchester Keratoconus Study (MKS), slit scanning CM was used to evaluate 29 keratoconic patients and light microscopy (LM) was performed on two of the keratoconic corneas post‐keratoplasty. The findings of the MKS are compared with other CM studies. Consideration of the differences between studies of cell counts is confounded by the use of different experimental controls. A consensus exists among studies with respect to qualitative observations. The epithelium appears more abnormal with increasing severity of keratoconus. In severe disease, the superficial epithelial cells are elongated and spindle shaped, epithelial wing cell nuclei are larger and more irregularly spaced and basal epithelial cells are flattened. Bowman’s layer is disrupted and split in the region of the cone and intermixed with epithelial cells and stromal keratocytes. Stromal haze and hyper‐reflectivity observed with CM correspond with apical scarring seen with the slitlamp biomicroscope (SLB). Hyper‐reflective keratocyte nuclei are thought to indicate the presence of fibroblastic cells. Increased haze detected with CM is found with LM to be due to fibroblastic accumulation and irregular collagen fibres. Dark stromal bands observed with CM correlate with the appearance of Vogt’s striae with SLB. Desçemet’s membrane appears normal with both CM and LM. Some evidence of endothelial cell elongation is observed with CM. The application of CM to ophthalmic practice has facilitated a greater understanding of medical and surgical approaches that are used to treat keratoconus. This review offers new perspectives on keratoconus and provides a framework, against which tissue changes in this visually debilitating condition can be studied in a clinical context in vivo using CM.
Spermatozoa isolated from cat testes retain their structural integrity as well as a developmental potential after refrigeration for up to 7 days

Summary The objective of this study was to compare the efficiency of preservation media for isolated feline testicular spermatozoa as well as the concentrations of bovine serum albumin (BSA) on: (1) the membrane (sperm membrane integrity (SMI)) and DNA integrity of spermatozoa; and (2) the developmental potential of spermatozoa after intracytoplasmic sperm injection (ICSI). Isolated cat spermatozoa were stored in HEPES-M199 medium (HM) or Dulbecco's phosphate-buffered saline (DPBS) at 4°C for up to 7 days. Results indicated that HM maintained a better SMI than DPBS throughout the storage periods (P > 0.05). When spermatozoa were stored in HM supplemented with BSA at different concentrations (4, 8 or 16 mg/ml), SMI obtained from HM containing 8 and 16 mg/ml BSA was higher than with 4 mg/ml BSA (P < 0.05). DNA integrity of spermatozoa stored in HM with 16 mg/ml BSA for 7 days was poorer than that of the fresh control, but the subsequent percentages of cleavage, morula, blastocyst produced by ICSI, as well as their average blastomere numbers of blastocysts, were similar (P > 0.05). In summary, cat spermatozoa immediately isolated from testicular tissue can be stored as a suspension in basic buffered medium at 4°C for up to 7 days. BSA supplementation into the medium improves membrane integrity of the spermatozoa during cold storage. Testicular spermatozoa stored in HM containing 16 mg/ml BSA retained full in vitro developmental potential after ICSI, similar to that of fresh controls even though DNA integrity had slightly declined.
Distinctions in lymphocyte responses to IL-2 and IL-15 reflect differential ligand binding interactions with the IL-2Rbeta chain and suggest differential roles for the IL-2Ralpha and IL-15Ralpha subunits.

More interleukin 15 (IL-15) than IL-2 was needed to generate comparable proliferative responses by phytohaemagglutinin (PHA) blasts and Tf-1beta cells expressing high affinity and intermediate affinity IL-2 receptor (IL-2R) complexes, respectively. The focus of these experiments was to determine the contribution of the shared IL-2 and IL-15 receptor components to these dose-response differences. Some of this difference can be attributed to the role of the IL-2Rbeta chain, in that HuMikbeta1, a monoclonal antibody recognizing the IL-2Rbeta chain, blocks 92.2+/-2.5% (mean+/-SE) of the IL-2 proliferative response by Tf-1beta cells but only inhibits 57.9+/-3.7% of the IL-15 response, indicating that IL-2 and IL-15 may physically utilize the IL-2Rbeta chain differently. Monoclonal antibody 341, which recognizes IL-2Rbeta but does not inhibit IL-2 binding to the IL-2Rbeta chain, blocks 35.4+/-2.3% of IL-15-stimulated proliferation of PHA blasts, while not affecting the IL-2-stimulated proliferation. Finally, although HuMikbeta1 does not inhibit IL-2 responses by PHA blasts bearing high affinity IL-2 receptors, HuMikbeta1 does block IL-15-stimulated proliferation by these same cells bearing high affinity IL-15 receptors (88.5+/-1.6% inhibition). This indicates that the role of IL-15Ralpha in the high affinity IL-15R complex is distinct from that of IL-2Ralpha in the high affinity IL-2R complex. Overall, these studies show that the physical interactions of the IL-2Rbetagammac complex with IL-2 are different than the interactions with IL-15.
Silicon ribbon cables for chronically implantable microelectrode arrays

Describes the design, fabrication, and testing of miniature ultraflexible ribbon cables for use with micromachined silicon microprobes capable of chronic recording and/or stimulation in the central nervous system (CNS). These interconnects are of critical importance in reliably linking these microelectrodes to the external world through a percutaneous connector. The silicon cables allow the realization of multilead, multistrand shielded local interconnects that are extremely flexible and yet strong enough to withstand normal handling and surgical manipulation. Cables 5 /spl mu/m thick, 1-5 cm long, and from 60 to 250 /spl mu/m wide have been fabricated with up to eight leads. The series lead resistance is typically 4 k/spl Omega//cm for polysilicon and 500 /spl Omega//cm for tantalum with shunt capacitance values of 5-10 pF/cm and an interlead capacitance below 10 fF/cm. Soak tests in buffered saline performed under electrical and mechanical stress have been underway for over three years and show subpicoampere leakage levels. Silicon microprobes with built-in ribbon cables have remained functional for up to one gear in the guinea pig CNS, recording driven single-unit activity and maintaining impedance levels in the 1-7 M /spl Omega/ range. <<ETX>>
Minorities in Medical School and National Medical Fellowships, Inc.: 50 Years and Counting

&NA; For more than 50 years, National Medical Fellowships, Inc (NMF) has been the only private national organization dedicated exclusively to increasing the numbers of minorities in medicine. In the 1920s, Franklin C. McLean, an eminent physician in Chicago, began working to include Negro physicians in high‐ranked hospital residencies. In 1946 he and his colleagues founded Provident Medical Associates (PMA), which later become National Medical Fellowships, Inc. During the late 1940s and 1950s, the challenge was to break down the barriers that prevented Negro physicians from training. In the 1950s, the NMF made steady progress in increasing the number of black physicians, but it was in the 1960s that the barriers to blacks in medical training began to fall and their numbers increased dramatically. In the 1970s the NMF expanded its focus to include all minorities underrepresented in medicine, and through its programs and the broad social changes in U.S. society, unprecedented proportions of blacks, Hispanics, and Native Americans entered medical training. In the 1980s the commitment to bring minority physicians into medicine deepened and broadened, yet in the late 1990s the progress of past decades is jeopardized by legal and administrative restrictions. Now, when the numbers of underrepresented minorities are declining, the need to maintain and expand programs such as those of the NMF is more urgent than ever.
Parkinson’s disease DBS: what, when, who and why? The time has come to tailor DBS targets

Deep brain stimulation (DBS) has recently been proven to be an effective therapy for medication-refractory symptoms of Parkinson’s disease. As the evidence base continues to evolve, many important issues have surfaced, including: what operation should be performed (brain target[s], unilateral vs bilateral, simultaneous vs staged); when to operate (how early is too early to intervene? ), who should be operated on (disease duration, age, symptom profiles and the use of the interdisciplinary screening team); and finally, why to operate (the rationale of surgery vs medication/apomorphine pumps/duodopa pumps/stem cell trials/gene therapy trials). We will address each of these critical issues, as well make the argument that a tailored approach to DBS and DBS targeting will best serve each potential candidate. We will review the multiple peer-reviewed studies and we will emphasize the recently available data from randomized DBS studies. We will argue that moving away from a single DBS target (e.g., subthalamic nucleus DBS) and a single approach to DBS methodology (e.g., bilateral simultaneous operations) is a reasonable next step for the Parkinson’s disease community. Following careful interdisciplinary DBS screening, a physician–patient discussion has the potential to establish a patient-centered and symptom-specific outcome for each potential DBS candidate. The interdisciplinary DBS team can function together to formulate and to consider an optimal and tailored approach. A tailored approach will allow for the consideration of the complex and numerous variables that may contribute to a positive or negative overall DBS outcome. We will review and provide expert commentary on a potential interdisciplinary approach to selecting unilateral or alternatively bilateral subthalamic nucleus or globus pallidus internus DBS. Our approach is aimed to maximize benefit(s) and minimize risk(s) in order to best tailor therapy for an individual patient.
A brain–computer interface based on self-regulation of gamma-oscillations in the superior parietal cortex

Objective. Brain–computer interface (BCI) systems are often based on motor- and/or sensory processes that are known to be impaired in late stages of amyotrophic lateral sclerosis (ALS). We propose a novel BCI designed for patients in late stages of ALS that only requires high-level cognitive processes to transmit information from the user to the BCI. Approach. We trained subjects via EEG-based neurofeedback to self-regulate the amplitude of gamma-oscillations in the superior parietal cortex (SPC). We argue that parietal gamma-oscillations are likely to be associated with high-level attentional processes, thereby providing a communication channel that does not rely on the integrity of sensory- and/or motor-pathways impaired in late stages of ALS. Main results. Healthy subjects quickly learned to self-regulate gamma-power in the SPC by alternating between states of focused attention and relaxed wakefulness, resulting in an average decoding accuracy of 70.2%. One locked-in ALS patient (ALS-FRS-R score of zero) achieved an average decoding accuracy significantly above chance-level though insufficient for communication (55.8%). Significance. Self-regulation of gamma-power in the SPC is a feasible paradigm for brain–computer interfacing and may be preserved in late stages of ALS. This provides a novel approach to testing whether completely locked-in ALS patients retain the capacity for goal-directed thinking.
Estrogen Receptor Binding to DNA Is Not Required for Its Activity through the Nonclassical AP1 Pathway*

In the classical signaling pathway, the estrogen receptor (ER) binds directly to estrogen response elements (EREs) to regulate gene transcription. To test the hypothesis that the nonclassical pathway involves ER interactions with other proteins rather than direct binding to DNA, mutations were introduced into the DNA binding domain (DBD) of the mouse ERα. The effects of these DBD mutations were examined in DNA binding assays using reporter constructs containing either EREs (classical) or AP1 (nonclassical) response elements. Using the AP1 reporter, there was a reversal of ER action relative to that seen with the ERE reporter. Estradiol induced suppression, and the antiestrogen ICI 182,780 stimulated transcription of the AP1 reporter. DBD mutations in the proximal (P-box) of the first zinc finger of the ER (E207A/G208A and E207G/G208S) eliminated ERE binding. These mutants were inactive using the ERE reporter but retained partial or full activity with the AP1 reporter. The DBD mutant ERs interacted with Jun when tested in mammalian cell two-hybrid assays. Two mutations (K366D and I362R) in the ER ligand binding domain known to alter coactivator interactions impaired transcriptional responses using either the ERE or AP1 reporters. We concluded that ER action through the AP1 response element involves interactions with other promoter-bound proteins instead of, or in addition to, direct binding to DNA. Interactions with coactivators were required for both pathways. These data supported a model in which ER-mediated transcriptional activation or repression is dependent on the ligand and the nature of the response element in the target gene.
Sleepiness and driving: the experience of UK car drivers

SUMMARY A postal questionnaire survey aimed at exploring the relationship between accidents and daytime sleepiness was sent to 9000 male drivers of which 4621 (51.3%) responded (mean age 47.7, SD 17.1). Drivers provided details of the accidents they had experienced in the last 3 y, and identified those factors, including tiredness, they thought contributed to the accident. In addition, drivers completed the Epworth scale measuring daytime sleepiness and reported whether they had felt close to falling asleep whilst driving during the past 12 mo. Analysis of the data showed that 29% of drivers had felt close to falling asleep at the wheel in the last 12 mo, the probability of which depended on Epworth score, age, occupational group, annual mileage, the proportion of time spent driving on motorways and in built‐up areas, how long the driver is prepared to drive before taking a break, and whether the driver is driving a company car o r not. Overall, about 7% of accident ‘involvements’ were associated with tiredness (representing 9‐10Y0 of accidents)‐a figure which is higher on motorways than on rural roads or built‐up roads and higher still in the early hours of the morning. Accident rates of company car drivers and for those who have felt close to falling asleep at the wheel in the last year are shown to be associated with daytime sleepiness. For example, a company car driver who has felt close to falling asleep at the wheel in the last 12 mo and who scores highly on the Epworth scale has an accident liability which is 70% higher than a similar driver who scores zero on the Epworth scale. Snoring every night increases accident liability by about 30%).
Cholinergic neurons of the chick ciliary ganglia express adrenergic traits in vivo and in vitro

In this study, we sought to determine whether neurons of the chick embryo ciliary ganglia (CG), a parasympathetic cholinergic ganglia, can express catecholaminergic (CA) traits. To accomplish this, we used immunocytochemical techniques to examine the presence of the CA enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) in CGs removed from chick embryo at day 8 of development (E8). Few neurons containing TH but not PNMT were found in the E8 CG. To examine whether CG neurons express CA enzymes in vitro, CGs removed from E8 chick embryo were dissociated and kept in culture for 3 to 12 days. In 50% of the culture dishes, some neurons contain TH or PNMT after 5 days in vitro. In an equal proportion of culture plates, CG neurons did not express the enzymes. To determine whether the proportion of CG neurons expressing TH or PNMT is increased by tissue influences, ganglion cells were co-cultured with notochord. In 90% of the co-culture experiments, most neurons present in the culture dishes stained with TH or PNMT after 5 days in vitro. To test for the presence of aromatic L-amino acid decarboxylase (AADC), another CA enzyme, cultures of CGs and CGs plus notochord were incubated with levodopa and processed for the detection of CA histofluorescence. Dopamine histofluorescence was present in all neurons after 3 days in vitro irrespective of the presence of notochord, suggesting that the expressions of TH and PNMT and that of AADC are differentially regulated. This study, therefore, demonstrates that cholinergic neurons of the CG contain CA enzymes in vivo and in vitro and that the proportion of neurons expressing CA traits during development in vitro can be increased by environmental cues such as those released by the notochord.
Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of human immunodeficiency virus type 1, using ten human monoclonal antibodies

Immunogenic regions of the gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) were previously mapped by examining polyclonal sera from HIV-infected patients and rodent polyclonal and monoclonal antibodies (MAbs) to peptides of gp41. To define the epitopes within these regions to which infected humans respond during the course of infection, the specificity of human MAbs to these regions had to be studied. Using 10 human MAbs identified initially by their reactivity to whole gp41 in HIV-1 lysates, the epitopes within the immunodominant region of gp41 and within a second immunogenic region of gp41 have been mapped. Thus, five MAbs (from five different patients) to the immunodominant domain of gp41 in the vicinity of the cysteines at positions 598 and 604 (hereinafter designated cluster I) reacted with a stretch of 11 amino acids from positions 590 to 600. Four of these five MAbs were reactive with linear epitopes, while one MAb required the conformation conferred by the disulfide bridge between the aforementioned cysteines. Three MAbs to cluster I revealed dissociation constants ranging from 10(-6) to 10(-8) M, depending on the MAb tested and the size of the synthetic or recombinant peptide used in the assay. Five additional MAbs reacted with a second immunogenic region between positions 644 and 663 (designated cluster II). Four of these five MAbs were specific for conformational determinants. Titration of sera from HIV-infected patients showed that there was about 100-fold more antibody to cluster I than to cluster II in patients' sera, confirming the immunodominance of cluster I.
Human centromere repositioning "in progress".

Centromere repositioning provides a potentially powerful evolutionary force for reproductive isolation and speciation, but the underlying mechanisms remain ill-defined. An attractive model is through the simultaneous inactivation of a normal centromere and the formation of a new centromere at a hitherto noncentromeric chromosomal location with minimal detrimental effect. We report a two-generation family in which the centromeric activity of one chromosome 4 has been relocated to a euchromatic site at 4q21.3 through the epigenetic formation of a neocentromere in otherwise cytogenetically normal and mitotically stable karyotypes. Strong epigenetic inactivation of the original centromere is suggested by retention of 1.3 megabases of centromeric alpha-satellite DNA, absence of detectable molecular alteration in chromosome 4-centromereproximal p- and q-arm sequences, and failure of the inactive centromere to be reactivated through extensive culturing or treatment with histone deacetylase inhibitor trichostatin A. The neocentromere binds functionally essential centromere proteins (CENP-A, CENP-C, CENP-E, CENP-I, BUB1, and HP1), although a moderate reduction in CENP-A binding and sister-chromatid cohesion compared with the typical centromeres suggests possible underlying structural/functional differences. The stable mitotic and meiotic transmissibility of this pseudodicentric-neocentric chromosome in healthy individuals and the ability of the neocentric activity to form in a euchromatic site in preference to a preexisting alphoid domain provide direct evidence for an inherent mechanism of human centromere repositioning and karyotype evolution "in progress. " We discuss the wider implication of such a mechanism for meiotic drive and the evolution of primate and other species.