Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct, Cross-Reactive Epitope Specificities of CD8 T Cell Responses Are Induced by Natural Hepatitis B Surface Antigen Variants of Different Hepatitis B Virus Genotypes1

We investigated the specific and cross-reactive CD8 T cell immunity to three natural variants (of different geno/serotype) of the small hepatitis B surface Ag (or S protein). The Dd-binding variants of the S201–209 epitope showed different immunogenicity. The loss of the consensus C-terminal (P9) anchor abrogated its immunogenicity. In contrast, a conservative (serine vs asparagine) exchange at P7 primed cross-reactive CD8 T cells that preferentially recognized the priming variant. Cross-reactive CD8 T cell responses to a variant could be primed in mice tolerant to an alternative variant of the Dd-binding S201–209 peptide. Loss of the C-terminal (P10) anchor in S185–194 eliminated its immunogenicity in HLA-A*0201(A2)-transgenic mice but two conservative exchanges (leucine vs valine in P2, and leucine vs isoleucine in P6) in S208–216 generated cross-reactive CD8 T cell responses with strong preference for the priming variant. Similar cross-reactive recognition of variant envelope epitopes were also found in S208–216-specific CD8 T cells from hepatitis B virus (HBV)-infected patients. Distinct CD8 T cell populations cross-reactive to natural variants of class I-restricted HBV epitopes can be primed by vaccination (of mice) or natural infection (of humans), and they may play a role in the “spontaneous remission” or the specific immunotherapy of chronic HBV infection.
Human CDC6/Cdc18 Associates with Orc1 and Cyclin-cdk and Is Selectively Eliminated from the Nucleus at the Onset of S Phase

ABSTRACT In a two-hybrid screen for proteins that interact with human PCNA, we identified and cloned a human protein (hCdc18) homologous to yeast CDC6/Cdc18 and human Orc1. Unlike yeast, in which the rapid and total destruction of CDC6/Cdc18 protein in S phase is a central feature of DNA replication, the total level of the human protein is unchanged throughout the cell cycle. Epitope-tagged protein is nuclear in G1 and cytoplasmic in S-phase cells, suggesting that DNA replication may be regulated by either the translocation of this protein between the nucleus and the cytoplasm or the selective degradation of the protein in the nucleus. Mutation of the only nuclear localization signal of this protein does not alter its nuclear localization, implying that the protein is translocated to the nucleus through its association with other nuclear proteins. Rapid elimination of the nuclear pool of this protein after the onset of DNA replication and its association with human Orc1 protein and cyclin-cdks supports its identification as human CDC6/Cdc18 protein.
Transcranial Direct Current Stimulation of the Medial Prefrontal Cortex Affects Judgments of Moral Violations

Previous studies show that neural activities in the medial prefrontal cortex (mPFC) are correlated with moral processing during picture viewing tasks. In this study, we applied transcranial direct current stimulation (tDCS) to determine whether this non-invasive brain stimulation technique could modulate the evaluation of moral violations. Sixty-four subjects were randomly recruited, separated into different groups and tested with 42 pairs of pictures depicting moral violations. Each subject was required to rate the pictures two separate times, i.e., before and after tDCS intervention. We found that anodal tDCS (atDCS) increases cortical excitability over the mPFC (between the Fpz and Fp1 positions) as well as the sense of morality and emotional arousal of the subjects. In conclusion, this study indicated that the mPFC plays an important role in moral judgments while modulating ratings of moral violations under tDCS intervention conditions.
Cooperation Enforcement Mechanism Considering Battery Cost in Ad hoc Networks

Mobile ad hoc networks have been an active research area for several years. So nodes' selfish behavior to save the battery for their own communication cannot be neglect. However, general cooperation enforcement mechanisms do not consider node battery, so hotspot node issue may exist; even badly lead to network separation. This paper proposes a kind of cooperation enforcement reputation mechanisms considering node battery in ad hoc networks. Theoretical analysis and numerical simulation results show that the reputation mechanism considering battery cost, comparing with the traditional reputation mechanisms, can prolong networks existence time and improve network throughput, but at the cost of a little more packets delay.
Gait Speed Predicts Incident Disability: A Pooled Analysis.

BACKGROUND Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function. METHODS We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking ¼ - ½ mile or climbing 10 steps within 3 years. RESULTS Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to ≥ 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10% to 1% in men, and from 15% to 1% in women, while mobility difficulty trended from 47% to 4% in men and 40% to 6% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve. CONCLUSION In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality.
Code review and cooperative pair programming best practice

We need ways to improve the code quality. Programmers have different level of tenure and experience. Standard and programming languages change and we are forced to re-use legacy code with minimum revision. Programmers develop their habits and can be slow to incorporate new technologies to simplify the code or improve the performance. We rolled out our customized code review and pair programming process to address these issues. The paper discusses the about the improvement of mandatory code review and pair programming practiced in the commercial software development, and also proposes effective approaches to customize the code review and pair programming to avoid the pitfalls and keep the benefits.
Substance Use and Attitudes on Professional Conduct Among Medical Students: A Single-Institution Study

ObjectiveThis study sought to examine how specific substance-use behavior, including nonmedical prescription stimulant (NPS) use, among U.S. medical students correlates with their attitudes and beliefs toward professionalism.MethodsA group of 74 students from Weill Cornell Medical College-New York and 32 from Weill Cornell Medical College-Qatar completed pre- and post-clerkship questionnaires assessing their attitudes toward psychiatry.ResultsAn anonymous survey was distributed to all medical students at a private medical university (46% response rate). Participants were asked to report alcohol and marijuana use patterns, NPS use, stress levels, and history of suicidal ideation. Results: Over one-third of medical students reported excessive drinking during the past month, and 5% reported NPS use during the past year. Students who endorsed such behavior were significantly less likely to view it as unprofessional and warranting intervention. A large number of students seemed unfamiliar with how to help a classmate with an NPS use problem.ConclusionsMedical students’ substance use behaviors appear to influence attitudes and beliefs toward professional issues regarding substance use.
The subpopulation of CF‐1 mice deficient in P‐glycoprotein contains a murine retroviral insertion in the mdr1a gene

A subpopulation of the CF‐1 mouse strain is sensitive to neurotoxicity following exposure to avermectins, a family of structurally related antiparasitic agents. This unusual sensitivity is the result of a deficiency in the mdr1a P‐glycoprotein that normally contributes to a functional blood‐brain barrier. Previous studies demonstrated a correlation between P‐glycoprotein levels in the brain, intestine, testis, and placenta with an restriction fragment length polymorphism (RFLP) pattern from DNA isolated from the animals. We have demonstrated that only P‐glycoprotein derived from the mdr1a gene is deficient in these mice. In this article, we describe the genetic defect in the subpopulation of CF‐1 mice resulting in an absence of P‐glycoprotein. The data presented describes a reverse transcription–polymerase chain reaction (RT‐PCR) protocol that specifically amplifies mdr1a mRNA from tissue and confirms that the P‐glycoprotein defect results from a truncated mRNA with a deleted exon 23. Genomic amplification and sequencing of the intron between exon 22 and 23 in Pgp‐deficient animals reveals an insertion of approximately 8.35 kb of DNA at the exon 23 intron–exon junction corresponding to a murine leukemia virus. This insertion results in the aberrant splicing of the mRNA and the loss of exon 23 during RNA processing. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:83–89, 2001
LDL‐receptor mutations in Europe

Familial hypercholesterolemia (FH) is a clinical definition for a remarkable increase of cholesterol serum concentration, presence of xanthomas, and an autosomal dominant trait of either increased serum cholesterol or premature coronary artery disease (CAD). The identification of the low‐density lipoprotein (LDL)‐receptor (LDLR) as the underlying cause and its genetic characterization in FH patients revealed more insights in the trafficking of LDL, which primarily transports cholesterol to hepatic and peripheral cells. Mutations within LDLR result in hypercholesterolemia and, subsequently, cholesterol deposition in humans to a variable degree. This confirms the pathogenetic role of LDLR and also highlights the existence of additional factors in determining the phenotype. Autosomal dominant FH is caused by LDLR deficiency and defective apolipoprotein B‐100 (APOB), respectively. Heterozygosity of the LDLR is relatively common (1:500). Clinical diagnosis is highly important and genetic diagnosis may be helpful, since treatment is usually effective for this otherwise fatal disease. Very recently, mutations in PCSK9 have been also shown to cause autosomal dominant hypercholesterolemia. For autosomal recessive hypercholesterolemia, mutations within the so‐called ARH gene encoding a cellular adaptor protein required for LDL transport have been identified. These insights emphasize the crucial importance of LDL metabolism intra‐ and extracellularly in determining LDL‐cholesterol serum concentration. Herein, we focus on the published European LDLR mutation data that reflect its heterogeneity and phenotypic penetrance. Hum Mutat 24:443–459, 2004. © 2004 Wiley‐Liss, Inc.
Intrinsic Josephson effects in Bi2Sr2CaCu2O8 single crystals.

We have observed Josephson coupling between CuO double layers in ${\mathrm{Bi}}_{2}$${\mathrm{Sr}}_{2}$${\mathrm{CaCu}}_{2}$${\mathrm{O}}_{8}$ single crystals by direct measurements of ac and dc Josephson effects with current flow along the c axis. The results show that a small ${\mathrm{Bi}}_{2}$${\mathrm{Sr}}_{2}$${\mathrm{CaCu}}_{2}$${\mathrm{O}}_{8}$ single crystal behaves like a series array of Josephson junctions which can exhibit mutual phase locking.
Consensus and controversy regarding osteoporosis in the pediatric population.

OBJECTIVE To review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence. METHODS The medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis. RESULTS Childhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass-variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients. CONCLUSION Bone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood.
Attachment of Proteus mirabilis to human urinary sediment epithelial cells in vitro is different from that of Escherichia coli

The in vitro attachment of 335 Proteus mirabilis strains from various human sources to human urinary tract epithelial cells was measured. No significant difference in adhesive capacity was found between P. mirabilis strains isolated from the blood of 89 patients with bacteremia, the stools of 36 healthy subjects and 56 patients with diarrhea, and the urine of 62 adults and 92 children with bacteriuria. High mean adhesion values were observed in all groups. The P. mirabilis strains attached only to squamous cells and not to transitional epithelial cells, whereas most of the Escherichia coli strains tested attached to both cell types; strains from patients with acute pyelonephritis attached more often than those from patients with acute cystitis or asymptomatic bacteriuria. The attachment of P. mirabilis to squamous epithelial cells was high about day 15 of the menstrual cycle of the epithelial cell donor, but low at the beginning and the end of the cycle. In contrast, the attachment of E. coli to squamous and transitional epithelial cells did not vary significantly with the menstrual cycle of the cell donor. Differences in adhesion characteristics of E. coli and P. mirabilis may relate to the differences in clinical appearance of urinary tract infections produced by the two organisms.
Stochastic Comparison on a Inventory System with Yield Uncertainty

In this paper we discuss the optimal problem on a discrete-time,single item, periodic review inventory system with yield and demand uncertainty, the main objective is to analyze how the uncertainty of yield rate and demand affect the optimal policy and cost in the system. For the single period case, by using the properties of stochastic ordering, the stochastic comparison results on the optimal inventory level and optimal expected cost are obtained. For the system with multi-period and with independent yield rates and demands in each period, by using the dynamic programming method, we show that the optimal inventory level is stochastic monotone in time period under a certain condition. The stochastic comparison results on the optimal cost for the inventory system with dependent yield rates and demands are also provided.
Palmitoylation of the synaptic vesicle fusion machinery

The fusion of synaptic vesicles with the pre‐synaptic plasma membrane mediates the secretion of neurotransmitters at nerve terminals. This pathway is regulated by an array of protein–protein interactions. Of central importance are the soluble NSF (N‐ethylmaleimide‐sensitive factor) attachment protein receptor (SNARE) proteins syntaxin 1 and SNAP25, which are associated with the pre‐synaptic plasma membrane and vesicle‐associated membrane protein (VAMP2), a synaptic vesicle SNARE. Syntaxin 1, SNAP25 and VAMP2 interact to form a tight complex bridging the vesicle and plasma membranes, which has been suggested to represent the minimal membrane fusion machinery. Synaptic vesicle fusion is stimulated by a rise in intraterminal Ca2+ levels, and a major Ca2+ sensor for vesicle fusion is synaptotagmin I. Synaptotagmin is likely to couple Ca2+ entry to vesicle fusion via Ca2+‐dependent and independent interactions with membrane phospholipids and the SNARE proteins. Intriguingly, syntaxin 1, SNAP25, VAMP2 and synaptotagmin I have all been reported to be modified by palmitoylation in neurons. In this review, we discuss the mechanisms and dynamics of palmitoylation of these proteins and speculate on how palmitoylation might contribute to the regulation of synaptic vesicle fusion.
Tuberculous meningitis in patients infected with the human immunodeficiency virus.

BACKGROUND AND METHODS Tuberculosis is a frequent complication of human immunodeficiency virus (HIV) infection. We describe the clinical manifestations and outcomes of tuberculous meningitis in patients with HIV infection, and compare them with those in non-HIV-infected patients. We reviewed the records from 1985 through 1990 at two large referral hospitals in Madrid for patients who had Mycobacterium tuberculosis isolated from cerebrospinal fluid. RESULTS Of 2205 patients with tuberculosis, 455 (21 percent) also had HIV infection, of whom 45 had M. tuberculosis isolated from the cerebrospinal fluid. Of the 37 HIV-infected patients with tuberculous meningitis for whom records were available, 24 (65 percent) had clinical or radiologic evidence of extrameningeal tuberculosis at the time of admission. In 18 of 26 patients (69 percent), a CT scan of the head was abnormal. In most patients, analysis of cerebrospinal fluid showed pleocytosis (median white-cell count, 0.234 x 10(9) per liter) and hypoglycorrhachia (median glucose level, 1.3 mmol per liter), but in 43 percent (15 of 35), the level of protein in cerebrospinal fluid was normal. In four patients with HIV infection, tuberculosis was only discovered after their deaths. Of the 33 patients who received antituberculous treatment, 7 died (in-hospital mortality, 21 percent). Illness lasting more than 14 days before admission and a CD4+ cell count of less than 0.2 x 10(9) per liter (200 per cubic millimeter) were associated with a poor prognosis. Comparison with tuberculous meningitis in patients without HIV infection showed that the presentation, clinical manifestations, cerebrospinal fluid findings, and mortality were generally similar in the two groups. However, of the 1750 patients without HIV infection, only 2 percent (38 patients) had tuberculous meningitis, as compared with 10 percent of the HIV-infected patients (P less than 0.001). CONCLUSIONS HIV-infected patients with tuberculosis are at increased risk for meningitis, but infection with HIV does not appear to change the clinical manifestations or the outcome of tuberculous meningitis.
Cetuximab plus FOLFOX for colorectal cancer (EXPLORE): Preliminary safety analysis of a randomized phase III trial.

3531 Background: The EXPLORE study is a randomized phase III study comparing cetuximab (Erbitux) plus FOLFOX4 (5-FU, leucovorin, oxaliplatin), to FOLFOX4 in 2nd-line metastatic, EGFR-positive colorectal cancer (CRC) patients (pts). Since this study is the first experience combining cetuximab with FOLFOX4, an early safety assessment was performed. METHODS The first stage of this randomized phase III trial restricted accrual to 40 pts at 10 centers to obtain an early assessment of safety. Pts with metastatic EGFR-positive CRC who had progressed on prior first-line irinotecan therapy with an ECOG performance status <2 were randomized to either Arm A (cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 weekly dose and FOLFOX4 d1,d2 q 2 weeks) or to Arm B (FOLFOX4 q 2 weeks). A pooled analysis of safety is presented. RESULTS Forty patients were randomized from March to November, 2003. They included 20 women and 20 men with a mean age of 61 years. Two patients did not receive study therapy and are excluded from the analysis. A total of 178 cycles were administered to the 38 pts with a median of 3 cycles per pt (range 1-15). There have been 4 disease-related deaths and one severe non-fatal hypersensitivity reaction (HSR). A summary table of adverse events associated with chemotherapy and cetuximab is below. The incidence and severity of these events appear comparable to previous reports of cetuximab with chemotherapy or of FOLFOX4. CONCLUSIONS In this pooled analysis the characteristic toxicities of cetuximab and FOLFOX4 do not appear to be increased. The study is continuing to accrue to its target of 1100 patients. [Figure: see text] [Table: see text].
Survey on certificateless key management schemes in mobile ad hoc networks

In order to ensure the security of mobile ad hoc networks (MANETs), the research on certificateless key management scheme is attracting more and more attention. The certificateless key management scheme can well resist the key escrow problem and it is very suitable for MANET, which is source-constrained and has no public key infrastructure. In this paper, we give an overview of some recent certificateless key management schemes and analyse their advantages and disadvantages. Then we make a comparison of their main methods, key distribution, private key generation and their calculation cost. Finally we put forward a suggestion to solve the problems existing in the certificateless key management scheme.
Membrane domains and polarized trafficking of sphingolipids.

The plasma membrane of polarized cells consists of distinct domains, the apical and basolateral membrane, that are characterized by a distinct lipid and protein content. Apical protein transport is largely mediated by (glyco)sphingolipid--cholesterol enriched membrane microdomains, so called rafts. In addition changes in the direction of polarized sphingolipid transport appear instrumental in cell polarity development. Knowledge is therefore required of the mechanisms that mediate sphingolipid sorting and the complexity of the trafficking pathways that are involved in polarized transport of both sphingolipids and proteins. Here we summarize specific biophysical properties that underly mechanisms relevant to sphingolipid sorting, cargo recruitment and polarized trafficking, and discuss the central role of a subapical compartment, SAC or common endosome (CE), as a major intracellular site involved in polarized sorting of sphingolipids, and in development and maintenance of membrane polarity.