Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation at Positively Selected Positions in the Binding Site for HLA-C Shows That KIR2DL1 Is a More Refined but Less Adaptable NK Cell Receptor Than KIR2DL3

Through recognition of HLA class I, killer cell Ig-like receptors (KIR) modulate NK cell functions in human immunity and reproduction. Although a minority of HLA-A and -B allotypes are KIR ligands, HLA-C allotypes dominate this regulation, because they all carry either the C1 epitope recognized by KIR2DL2/3 or the C2 epitope recognized by KIR2DL1. The C1 epitope and C1-specific KIR evolved first, followed several million years later by the C2 epitope and C2-specific KIR. Strong, varying selection pressure on NK cell functions drove the diversification and divergence of hominid KIR, with six positions in the HLA class I binding site of KIR being targets for positive diversifying selection. Introducing each naturally occurring residue at these positions into KIR2DL1 and KIR2DL3 produced 38 point mutants that were tested for binding to 95 HLA- A, -B, and -C allotypes. Modulating specificity for HLA-C is position 44, whereas positions 71 and 131 control cross-reactivity with HLA-A*11:02. Dominating avidity modulation is position 70, with lesser contributions from positions 68 and 182. KIR2DL3 has lower avidity and broader specificity than KIR2DL1. Mutation could increase the avidity and change the specificity of KIR2DL3, whereas KIR2DL1 specificity was resistant to mutation, and its avidity could only be lowered. The contrasting inflexibility of KIR2DL1 and adaptability of KIR2DL3 fit with C2-specific KIR having evolved from C1-specific KIR, and not vice versa. Substitutions restricted to activating KIR all reduced the avidity of KIR2DL1 and KIR2DL3, further evidence that activating KIR function often becomes subject to selective attenuation.
Laminectomy versus percutaneous electrode placement for spinal cord stimulation.

OBJECTIVE The purpose of this study was to compare the long-term effectiveness of spinal cord stimulation using laminectomy-style electrodes versus that using percutaneously implanted electrodes. METHODS Forty-one patients underwent an initial trial period of spinal cord stimulation with temporary electrodes at Duke Medical Center between December 1992 and January 1998. A permanent system was implanted if trial stimulation reduced the patient's pain by more than 50%. Median long-term follow-up after permanent electrode placement was 34 months (range, 6-66 mo). Severity of pain was determined postoperatively by a disinterested third party using a visual analog scale and a modified outcome scale. RESULTS Twenty-seven (66%) of the 41 patients participating in the trial had permanent electrodes placed. Visual analog scores decreased an average of 4.6 among patients in whom electrodes were placed via laminectomy in the thoracic region (two-tailed t test, P < 0.0001). Patients who underwent percutaneous placement of thoracic electrodes had an average decrease of 3.1 in their visual analog scores (two-tailed t test, P < 0.001). Electrodes placed through laminectomy furnished significantly greater long-term pain relief than did those placed percutaneously, as measured by a four-tier outcome grading scale (P = 0.02). CONCLUSION Spinal cord stimulation is an effective treatment for chronic pain in the lower back and lower extremities that is refractory to conservative therapy. Electrodes placed via laminectomy in the thoracic region appear to be associated with significantly better long-term effectiveness than are electrodes placed percutaneously.
The feasibility of fast charging in Dutch cities: The technological, economical, social and political factors explained

The introduction of electric vehicles (EVs) can significantly reduce greenhouse gas emissions, fossil fuel depletion and urban air pollution. The exponential growth of the EV market requires a significant expansion of the public charging infrastructure. This causes challenges especially in cities in terms of parking pressure, grid reinforcements and investment costs. There are two charging technologies for electric vehicles: normal charging and fast charging. Fast charging technology is developing rapidly, with charging speeds that allow a full charge in fifteen minutes in 2020. Local governments however, currently mainly support and subsidise normal charging. Currently, there is no scientific study that combines the technical, economical, social and political perspectives to evaluate the feasibility of fast charging. This research determines the current and future feasibility of fast charging in Dutch cities. An exploratory case study of the major Dutch cities of Amsterdam, Rotterdam, The Hague and Utrecht is performed. The political economy theory on transport innovations by Feitelson and Salomon is used as the theoretical perspective. From the research it is concluded that fast charging is increasingly feasible as a charging solution in Dutch cities. Currently, there is a focus on normal charging in cities caused by the current EVs and charging technology. The developments sparked by larger batteries and faster charging however increase the feasibility of fast charging. As EV adoption accelerates, a more hybrid mix of normal and fast charging solutions is needed in crowded cities to accommodate the charging needs. The increasing industry interest, consumer attitude and high charging capacity make fast charging an important factor in the future public charging infrastructure.
Migraine in the Andes and Headache at Sea Level

In Cerro de Pasco (CP), Peru (altitude 4338 m) 24% of men have migraine with aura. We studied 30 men. Twenty CP natives, examined in CP, were rated using a chronic mountain sickness (CMS) score to separate controls (10) from those with CMS (10), a maladaptation syndrome in natives to altitude which includes severe, recurring headache. We collected white cells in CP and, from the same men, within 1 h of arrival in Lima (150 m above sea level). Ten normal US men volunteered white cells for comparison. After RNA extraction we assessed gene expression by reverse transcription-polymerase chain reaction. Low ATP1A1 subunit of the ATPase gene mRNA expression in CP was correlated with headache (P = 0.002), acral paraesthesias (P = 0.004) and CMS score (P < 0.001). ATP1A1 subunit expression was increased in all Andeans in Lima (P < 0.001). There were no differences between Andean controls in Lima and US controls. Manipulation of Na+/K+ATPase could offer relief for migraineurs at sea level.
Partial purification of rat hepatic stimulator substance and characterization of its action on hepatoma cells and normal hepatocytes

The active principle of a cytosol extract from weanling rat liver representing a putative liver‐specific growth factor was partially purified and characterized. “Hepatic stimulator substance” was extracted from the livers of 40‐ to 60‐gm male rats by heat treatment of a homogenate in 35% (w/v) phosphate‐buffered saline and subsequent ultracentrifugation. This “heat supernatant” and fractions derived from the subsequent purification steps were tested for growth stimulatory activity in two rat hepatoma cell lines. The undifferentiated, fibroblas‐toid‐like HTC hepatoma cells did not respond to crude hepatic stimulator substance or any of the partially purified preparations. In contrast, MH1C1 cells, which display some differentiated hepatic functions and epithelial morphology, reacted to hepatic stimulator substance and the purified fractions with a dose‐dependent increase of their growth rate in serum‐free culture. Although insulin, glucagon and epidermal growth factor showed only a minor effect on MH1C1 cell growth on their own, they were active as permissive or potentiating factors for the expression of the maximal effect of hepatic stimulator substance. Similarly, normal adult rat hepatocytes were only sensitive to hepatic stimulator substance when cultured in the simultaneous presence of epidermal growth factor. Under such conditions, hepatic stimulator substance stimulated hepatocyte entry into the S‐phase of the cell cycle 3‐fold compared to epidermal growth factor alone. Hepatic stimulator substance did not affect growth of human skin fibroblasts and of the rat intestinal crypt cell line IEC‐6. When compared to the supernatant obtained after a 65°C heat step, heating to 95°C increased the biological activity of the extract 2‐ to 3‐ fold. MH1C1 cell growth with 50 μg protein per ml of the 95°C heat supernatant in serum‐free medium was identical to the growth rate obtained with 10% fetal bovine serum. Precipitation with ethanol reduced the growth‐stimulatory activity of hepatic stimulator substance by 60%. The biological activity was concentrated 10‐ and 100‐fold by conventional and high‐performance gel filtration, respectively. The biological activity was non‐dialyzable and was destroyed by protease treatment. In sodium dodecyl slfate‐polyacrylamide gel electrophoresis, the partially purified material showed three bands between M.W. 15,300 and 20,000.
Int6 and Moe1 interact with Cdc48 to regulate ERAD and proper chromosome segregation

Int6/eIF3e is implicated in tumorigenesis, but its molecular functions remain unclear. We have studied its fission yeast homolog Yin6, reporting that it regulates proteolysis by controlling the assembly/localization of proteasomes, and binds directly to another conserved protein, Moe1. In the present study, we isolated Cdc48 as a Moe1-binding protein from a yeast two-hybrid screen, and confirmed biochemically that they form a stable complex in fission yeast. Overexpressing Moe1 or Yin6 partially rescued phenotypes of cdc48 mutants; conversely, overexpressing Cdc48 partially rescued phenotypes of moe1 or yin6 mutants. Mutants defective in both Cdc48 and the Yin6-Moe1 complex showed growth defects that were far more severe than either alone. These double mutants were severely deficient in endoplasmic reticulum associated degradation (ERAD), as they were hypersensitive to accumulation of misfolded proteins. In addition, their chromosomes showed frequent defects in spindle attachment and segregation — these mitotic defects correlated with Ase1 and Bir1/survivin mislocalization. These results suggest that Cdc48, Yin6, and Moe1 act in the same protein complex to concertedly control ERAD and chromosome segregation. Many of these properties are evolutionarily conserved in humans, since human Cdc48 rescued the lethality of the yeast cdc48∆ mutant, and Int6 and Moe1/eIF3d bind Cdc48 in human cells.
Coinfecting Prion Strains Compete for a Limiting Cellular Resource

ABSTRACT Prion strain interference can influence the emergence of a dominant strain from a mixture; however, the mechanisms underlying prion strain interference are poorly understood. In our model of strain interference, inoculation of the sciatic nerve with the drowsy (DY) strain of the transmissible mink encephalopathy (TME) agent prior to superinfection with the hyper (HY) strain of TME can completely block HY TME from causing disease. We show here that the deposition of PrPSc, in the absence of neuronal loss or spongiform change, in the central nervous system corresponds with the ability of DY TME to block HY TME infection. This suggests that DY TME agent-induced damage is not responsible for strain interference but rather prions compete for a cellular resource. We show that protein misfolding cyclic amplification (PMCA) of DY and HY TME maintains the strain-specific properties of PrPSc and replicates infectious agent and that DY TME can interfere, or completely block, the emergence of HY TME. DY PrPSc does not convert all of the available PrPC to PrPSc in PMCA, suggesting the mechanism of prion strain interference is due to the sequestering of PrPC and/or other cellular components required for prion conversion. The emergence of HY TME in PMCA was controlled by the initial ratio of the TME agents. A higher ratio of DY to HY TME agent is required for complete blockage of HY TME in PMCA compared to several previous in vivo studies, suggesting that HY TME persists in animals coinfected with the two strains. This was confirmed by PMCA detection of HY PrPSc in animals where DY TME had completely blocked HY TME from causing disease.
Adipose-Derived Stem Cells in Novel Approaches to Breast Reconstruction: Their Suitability for Tissue Engineering and Oncological Safety

Adipose-derived stem cells (ADSCs) are rapidly becoming the gold standard cell source for tissue engineering strategies and hold great potential for novel breast reconstruction strategies. However, their use in patients with breast cancer is controversial and their oncological safety, particularly in relation to local disease recurrence, has been questioned. In vitro, in vivo, and clinical studies using ADSCs report conflicting data on their suitability for adipose tissue regeneration in patients with cancer. This review aims to provide an overview of the potential role for ADSCs in breast reconstruction and to examine the evidence relating to the oncologic safety of their use in patients with breast cancer.
A Monoclonal Antibody Against Neem Leaf Glycoprotein Recognizes Carcinoembryonic Antigen (CEA) and Restricts CEA Expressing Tumor Growth

Carcinoembryonic antigen (CEA) is one of the promising tumor antigens mainly associated with carcinoma of the colon, lung, breast, etc. and received wide attention for cancer immunotherapy. Neem leaf glycoprotein (NLGP), an effective immunomodulator, is able to generate humoral and cellular immune responses in murine tumor models. We have generated a monoclonal antibody (mAb) against NLGP by fusing NLGP-immunized mice splenocytes with nonsecretory myeloma cells. A highly anti-NLGP mAb secreting clone (1C8; IgG2a in nature) has been identified and propagated in culture. 1C8 recognizes human CEA as good as NLGP by enzyme linked immunosorbent assay, Western blotting, and immunoprecipitation. 1C8 detects CEA on colon cancer tissues by immunochistochemistry. By flow cytometry, 1C8 specifically reacts with CEA+ human (Colo-205, HCT-116, and HT-29) and mouse (CT-26) colon cancer cells, but it showed minimum reactivity with CEA− human (MCF7, SiHa, and SCC084) and mouse (B16MelF10) cancer cells. This anti-NLGP 1C8 mAb revealed significant antitumor activity and better survivability in vivo in animals bearing mouse (CT-26 in BALB/c) and human (Colo-205 in athymic nude) CEA+ cancer cells. 1C8 has no direct influence on proliferation and migration of CEA+ cells, however, NK cell–dependent strong antibody-dependent cellular cytotoxicity reaction toward CEA+ cells and normalization of angiogenesis are chiefly associated with tumor growth restriction. Obtained results provided a new immunotherapeutic approach for the effective management of CEA+ tumors.
Role of Thylakoid ATP/ADP Carrier in Photoinhibition and Photoprotection of Photosystem II in Arabidopsis1[W][OA]

The chloroplast thylakoid ATP/ADP carrier (TAAC) belongs to the mitochondrial carrier superfamily and supplies the thylakoid lumen with stromal ATP in exchange for ADP. Here, we investigate the physiological consequences of TAAC depletion in Arabidopsis (Arabidopsis thaliana). We show that the deficiency of TAAC in two T-DNA insertion lines does not modify the chloroplast ultrastructure, the relative amounts of photosynthetic proteins, the pigment composition, and the photosynthetic activity. Under growth light conditions, the mutants initially displayed similar shoot weight, but lower when reaching full development, and were less tolerant to high light conditions in comparison with the wild type. These observations prompted us to study in more detail the effects of TAAC depletion on photoinhibition and photoprotection of the photosystem II (PSII) complex. The steady-state phosphorylation levels of PSII proteins were not affected, but the degradation of the reaction center II D1 protein was blocked, and decreased amounts of CP43-less PSII monomers were detected in the mutants. Besides this, the mutant leaves displayed a transiently higher nonphotochemical quenching of chlorophyll fluorescence than the wild-type leaves, especially at low light. This may be attributed to the accumulation in the absence of TAAC of a higher electrochemical H+ gradient in the first minutes of illumination, which more efficiently activates photoprotective xanthophyll cycle-dependent and independent mechanisms. Based on these results, we propose that TAAC plays a critical role in the disassembly steps during PSII repair and in addition may balance the trans-thylakoid electrochemical H+ gradient storage.
Does women’s empowerment through policy intervention reduce food insecurity in South Africa?

ABSTRACT This article determines the extent to which the food insecurity status of women in South Africa can be reduced by participating in gardening around the homestead, using survey data from 207 women farmers. A household food insecurity average score index and an empirical model that accounts for observed and unobserved factors contributing to food insecurity were employed. The findings reveal that participating in the programme worked to reduce the food insecurity of women significantly, and also show other policy factors that need to be taken into consideration to reduce food insecurity. We recommend that policy interventions towards promoting high participation by women are a sustainable strategy to address food insecurity and to achieve the 2030 agenda targeting an end to poverty and hunger.
Age‐Related Differences in the Lifestyle Regularity of Seniors Experiencing Bereavement, Care‐Giving, Insomnia, and Advancement Into Old‐Old Age

Compared to younger adults, seniors (≥60 yrs) often adopt a highly regular lifestyle, perhaps as an adaptive response to age‐related changes in their sleep and circadian rhythms. At baseline, diary measures of lifestyle regularity (SRM‐5) were obtained from 104 seniors of three separate groups. Thirty‐three subjects were challenged by spousal bereavement or the need to care for a spouse at home with dementia (Challenged); 33 were suffering from formally diagnosed (DSM‐IV) insomnia (Insomnia); and 38 were healthy, well‐functioning older seniors in the second half of their eighth decade of life or later (Healthy Older). The objective of this study was to determine whether lifestyle regularity increased as a function of age within each of these three senior groups. Overall, age was significantly correlated with SRM‐5 (r=0.41, p<0.001), with the SRM score increasing by 0.67 units/decade. The same was true for the Challenged and Insomnia groups, which also showed a significant correlation between SRM and age (Challenged: r=0.48, p<0.01; Insomnia: r=0.36, p<0.05), though with a slightly faster rate of SRM increase in the Challenged (0.95 units/decade) than Insomnia (0.55 units/decade) group. Perhaps there was no correlation between age and SRM (r=0.07, n.s.) in the Healthy Older group due to the small age range, although this group did have a higher overall SRM score than the other two groups (p<0.01). The study thus confirmed that the previously observed increase in lifestyle regularity over the adult lifespan persists into later life. This may represent an adaptive behavioral response that might be used in future therapeutic approaches.
Extraordinary Optical Transmission: Fundamentals and Applications

Extraordinary optical transmission (EOT) is a term that refers to electromagnetic resonances through sets of subwavelength apertures in either a flat or a corrugated metal film, providing a larger transmission of electromagnetic fields than would be expected from the small aperture size. Since its discovery in 1998, EOT has been a very active research field, leading both to the discovery of new ways of enhancing optical transmission and to its application to sensing, color filters, metamaterials, lenses, optical trapping, enhancement of nonlinear effects, among others. This paper reviews the different mechanisms that lead to EOT, paying special attention to the new research areas and applications that have appeared in the last few years.
Expanding the Andersen model: the role of psychosocial factors in long-term care use.

OBJECTIVE To examine a prevailing conceptual model of health services use (Andersen 1995) and to suggest modifications that may enhance its explanatory power when applied to empirical studies of race/ethnicity and long-term care. STUDY SETTING Twelve focus groups of African-American (five groups) and white (seven groups) individuals, aged 65 and older, residing in Connecticut during 2000. STUDY DESIGN Using qualitative analysis, data were coded and analyzed in NUD-IST 4 software to facilitate the reporting of recurrent themes, supporting quotations, and links among the themes for developing the conceptual framework. Specific analysis was conducted to assess distinctions in common themes between African-American and white focus groups. DATA COLLECTION Data were collected using a standardized discussion guide, augmented by prompts for clarification. Audio taped sessions were transcribed and independently coded by investigators and crosschecked to enhance coding validity. An audit trail was maintained to document analytic decisions during data analysis and interpretation. PRINCIPAL FINDINGS Psychosocial factors (e.g., attitudes and knowledge, social norms, and perceived control) are identified as determinants of service use, thereby expanding the Andersen model (1995). African-American and white focus group members differed in their reported accessibility of information about long-term care, social norms concerning caregiving expectations and burden, and concerns of privacy and self-determination. CONCLUSIONS More comprehensive identification of psychosocial factors may enhance our understanding of the complex role of race/ethnicity in long-term care use as well as the effectiveness of policies and programs designed to address disparities in long-term care service use among minority and nonminority groups.
Implementation of a mental spelling system based on steady-state visual evoked potential (SSVEP)

In this study, we implemented a new mental spelling system based on steady-state visual evoked potential (SSVEP), adopting a QWERTY style layout keyboard with 30 LEDs flickering with different frequencies. During the offline experiments performed with five participants, we optimized various factors influencing the performance of the mental spelling system, such as distances between adjacent keys, light source arrangements, stimulating frequencies, recording electrodes, and visual angles. The online experiments were conducted with six participants to verify the feasibility of the optimized mental spelling system. The results of the online experiments were an average typing speed of 9.39 letters per minute (LPM) with an average success rate of 87.58 % corresponding to an average information transfer rate of 40.72 bits per minute, demonstrating the high performance of the developed mental spelling system. Indeed, the average typing speed of 9.39 LPM attained in this study was one of the best LPM results among those reported in previous BCI literatures. To further enhance the performance of our mental spelling system, we combined eye direction information (‘left’ or ‘right’) extracted from a web camera with the SSVEP responses. As a result of the online experiments performed with 10 participants, the hybrid speller could reduce 16.6 typing errors on average.