Miracle-dz/UniFAR-FTUs huggingface dataset:
4.8 A 28nm x86 APU optimized for power and area efficiency

Carrizo (CZ, Fig. 4.8.7) is AMD's next-generation mobile performance accelerated processing unit (APU), which includes four Excavator (XV) processor cores and eight Radeon™ graphics core next (GCN) cores, implemented in a 28nm HKMG planar dual-oxide FET technology featuring 3 Vts of thin-oxide devices and 12 layers of Cu-based metallization. This 28nm technology is a density-focused version of the 28nm technology used by Steamroller (SR) [1] featuring eight 1× metals for dense routing, one 2× and one 4× for low-RC routing and two 16x metals for power distribution.
Regulatory T Cells Promote Natural Killer Cell Education in Mixed Chimeras

Therapeutic administration of regulatory T cells (Tregs) leads to engraftment of conventional doses of allogeneic bone marrow (BM) in nonirradiated recipient mice conditioned with costimulation blockade and mammalian target of rapamycin inhibition. The mode of action responsible for this Treg effect is poorly understood but may encompass the control of costimulation blockade–resistant natural killer (NK) cells. We show that transient NK cell depletion at the time of BM transplantation led to BM engraftment and persistent chimerism without Treg transfer but failed to induce skin graft tolerance. In contrast, the permanent absence of anti–donor NK reactivity in mice grafted with F1 BM was associated with both chimerism and tolerance comparable to Treg therapy, implying that NK cell tolerization is a critical mechanism of Treg therapy. Indeed, NK cells of Treg‐treated BM recipients reshaped their receptor repertoire in the presence of donor MHC in a manner suggesting attenuated donor reactivity. These results indicate that adoptively transferred Tregs prevent BM rejection, at least in part, by suppressing NK cells and promote tolerance by regulating the appearance of NK cells expressing activating receptors to donor class I MHC.
Interview with Dr. Maurizio C. Capogrossi regarding Pivotal Advance: High‐mobility group box 1 protein—a cytokine with a role in cardiac repair

Advance: High-mobility group box 1 protein—a cytokine with a role in cardiac repair Helene F. Rosenberg* and Joost J. Oppenheim *Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA; and Laboratory of Molecular Immunoregulation, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA
Batf3‐independent langerin− CX3CR1− CD8α+ splenic DCs represent a precursor for classical cross‐presenting CD8α+ DCs

This study tests the hypothesis that CD8α+ DCs in the spleen of mice contain an immature precursor for functionally mature, “classical” cross‐presenting CD8α+ DCs. The lymphoid tissues contain a network of phenotypically distinct DCs with unique roles in surveillance and immunity. Splenic CD8α+ DCs have been shown to exhibit a heightened capacity for phagocytosis of cellular material, secretion of IL‐12, and cross‐priming of CD8+ T cells. However, this population can be subdivided further on the basis of expression of both langerin/CD207 and CX3CR1. We therefore evaluated the functional capacities of these different subsets. The CX3CR1+ CD8α+ DC subset does not express langerin and does not exhibit the classical features above. The CX3CR1− CD8α+ DC can be divided into langerin‐positive and negative populations, both of which express DEC205, Clec9A, and high basal levels of CD86. However, the langerin+ CX3CR1− CD8α+ subset has a superior capacity for acquiring cellular material and producing IL‐12 and is more susceptible to activation‐induced cell death. Significantly, following purification and adoptive transfer into new hosts, the langerin− CX3CR1− CD8α+ subset survives longer, up‐regulates expression of langerin, and becomes more susceptible to activation‐induced cell death. Last, in contrast to langerin+ CX3CR1− CD8α+, the langerin− CX3CR1− CD8α+ are still present in Batf3−/− mice. We conclude that the classical attributes of CD8α+ DC are confined primarily to the langerin+ CX3CR1− CD8α+ DC population and that the langerin− CX3CR1− subset represents a Batf3‐independent precursor to this mature population.
5.2 A 118dB-PSRR 0.00067%(−103.5dB) THD+N and 3.1W fully differential class-D audio amplifier with PWM common-mode control

A high power-supply rejection ratio (PSRR) and high-linearity Class-D audio amplifier (CDA) becomes important as the CDA is directly connected to a battery supply for efficiency considerations in mobile phone applications. Several closed-loop pulse-width-modulation (PWM) CDAs with high PSRR (>90dB) have been published recently. In conventional PWM fully differential CDAs [1,2], these designs are focused on increasing differential loop gain to improve PSRR. However, the PSRR is mainly limited by feedback gain-matching, that is, resistor matching of the feedback network; hence, it is difficult to achieve PSRR >80dB for yield >99%. In [3], a pseudo-differential structure composed of two single-ended opamps is adopted to achieve PSRR >90dB. Nevertheless, it suffers from 3dB noise increase as compared to the fully differential counterpart. Moreover, unity-gain bandwidth (GBW) of single-ended opamps is usually smaller than that of fully differential opamps due to the design trade-off between noise and the location of current-mirror poles; hence, it results in low in-band gain and high total harmonic distortions (THDs) of pseudo-differential CDAs. As for linearity, conventional PWM CDAs suffer from poor linearity due to in-band aliasing tones. In the uniform PWM (UPWM) architecture [4] that achieves THD+N of around -96.5dB, a sinc function, realized by using a sample-and-hold circuit in front of the loop filter, is applied to avoid the signal-dependent intermodulations folding back in-band. However, high switching frequency is required and the power consumption is increased.
Chemical transformations during aging of zerovalent iron nanoparticles in the presence of common groundwater dissolved constituents.

Nanoscale zerovalent iron (NZVI) that was aged in simulated groundwater was evaluated for alterations in composition and speciation over 6 months to understand the possible transformations NZVI could undergo in natural waters. NZVI was exposed to 10 mN of various common groundwater anions (Cl(-), NO(3)(-), SO(4)(2-), HPO(4)(2-), and HCO(3)(-)) or to dissolved oxygen (saturated, approximately 9 mg/L). Fresh and exposed NZVI samples, along with Fe-oxide model compounds, were then analyzed using synchrotron radiation X-ray absorption spectroscopy (XAS) to yield both relative oxidation state, using the X-ray absorption near edge structure (XANES), and quantitative speciation information regarding the types and proportions of mineral species present, from analysis of the extended X-ray absorption fine structure (EXAFS). Over 1 month of aging the dissolved anions inhibited the oxidation of the NZVI to varying degrees. Aging for 6 months, however, resulted in average oxidation states that were similar to each other regardless of the anion used, except for nitrate. Nitrate passivated the NZVI surface such that even after 6 months of aging the particles retained nearly the same mineral and Fe(0) content as fresh NZVI. Linear least-squares combination fitting (LCF) of the EXAFS spectra for 1 month-aged samples indicated that the oxidized particles remain predominantly a binary phase system containing Fe(0) and Fe(3)O(4), while the 6 month aged samples contained additional mineral phases such as vivianite (Fe(3)(PO(4))(2). 8H(2)O) and iron sulfate species, possibly schwertmannite (Fe(3+)(16)O(16)(OH,SO(4))(12-13). 10-12H(2)O). The presence of these additional mineral species was confirmed using synchrotron-based X-ray diffraction (XRD). NZVI exposed to water saturated with dissolved oxygen showed a rapid (<24 h) loss of Fe(0) and evolved both magnetite and maghemite (gamma-Fe(2)O(3)) within the oxide layer. These findings have implications toward the eventual fate, transport, and toxicity of NZVI used for groundwater remediation.
Soluble β‐glucan from Grifola frondosa induces tumor regression in synergy with TLR9 agonist via dendritic cell‐mediated immunity

The maturation of dendritic cells into more‐immunostimulatory dendritic cells by stimulation with different combinations of immunologic agents is expected to provide efficient, adoptive immunotherapy against cancer. Soluble β‐glucan maitake D‐fraction, extracted from the maitake mushroom Grifola frondosa, acts as a potent immunotherapeutic agent, eliciting innate and adoptive immune responses, thereby contributing to its antitumor activity. Here, we evaluated the efficacy of maitake D‐fraction, in combination with a Toll‐like receptor agonist, to treat tumors in a murine model. Our results showed that maitake D‐fraction, in combination with the Toll‐like receptor 9 agonist, cytosine–phosphate–guanine oligodeoxynucleotide, synergistically increased the expression of dendritic cell maturation markers and interleukin‐12 production in dendritic cells, but it did not increase interleukin‐10 production, generating strong effector dendritic cells with an augmented capacity for efficiently priming an antigen‐specific, T helper 1–type T cell response. Maitake D‐fraction enhances cytosine–phosphate–guanine oligodeoxynucleotide‐induced dendritic cell maturation and cytokine responses in a dectin‐1–dependent pathway. We further showed that a combination therapy using cytosine–phosphate–guanine oligodeoxynucleotide and maitake D‐fraction was highly effective, either as adjuvants for dendritic cell vaccination or by direct administration against murine tumor. Therapeutic responses to direct administration were associated with increased CD11c+ dendritic cells in the tumor site and the induction of interferon‐γ–producing CD4+ and CD8+ T cells. Our results indicate that maitake D‐fraction and cytosine–phosphate–guanine oligodeoxynucleotide synergistically activated dendritic cells, resulting in tumor regression via an antitumor T helper cell 1–type response. Our findings provide the basis for a potent antitumor therapy using a novel combination of immunologic agents for future clinical immunotherapy studies in patients.
Myosin‐IIA regulates leukemia engraftment and brain infiltration in a mouse model of acute lymphoblastic leukemia

Leukemia dissemination (the spread of leukemia cells from the bone marrow) and relapse are associated with poor prognosis. Often, relapse occurs in peripheral organs, such as the CNS, which acts as a sanctuary site for leukemia cells to escape anti‐cancer treatments. Similar to normal leukocyte migration, leukemia dissemination entails migration of cells from the blood circulation into tissues by extravasation. To extravasate, leukemia cells cross through vascular endothelial walls via a process called transendothelial migration, which requires cytoskeletal remodeling. However, the specific molecular players in leukemia extravasation are not fully known. We examined the role of myosin‐IIA a cytoskeletal class II myosin motor protein, in leukemia progression and dissemination into the CNS by use of a mouse model of Bcr‐Abl‐driven B cell acute lymphoblastic leukemia. Small hairpin RNA‐mediated depletion of myosin‐IIA did not affect apoptosis or the growth rate of B cell acute lymphoblastic leukemia cells. However, in an in vivo leukemia transfer model, myosin‐IIA depletion slowed leukemia progression and prolonged survival, in part, by reducing the ability of B cell acute lymphoblastic leukemia cells to engraft efficiently. Finally, myosin‐IIA inhibition, either by small hairpin RNA depletion or chemical inhibition by blebbistatin, drastically reduced CNS infiltration of leukemia cells. The effects on leukemia cell entry into tissues were mostly a result of the requirement for myosin‐IIA to enable leukemia cells to complete the transendothelial migration process during extravasation. Overall, our data implicate myosin‐IIA as a key mediator of leukemia cell migration, making it a promising target to inhibit leukemia dissemination in vivo and potentially reduce leukemia relapses.
12.1 A rational-conversion-ratio switched-capacitor DC-DC converter using negative-output feedback

Switched-capacitor (SC) DC-DC converters have several advantages over inductive DC-DC converters in that they are easily integrated on-chip and can scale to desired power levels, rendering themselves promising for integrated voltage regulators, especially for small, low-power systems. However, many SC DC-DC converters offer only a few conversion ratios, limiting their use for systems in which either the input or output voltages vary. This is particularly important in wireless systems where battery voltage degrades slowly. [1] proposed a technique to reconfigure cascaded SC converters to achieve arbitrary binary ratios: p/2N, 0<;p<;2N, where N is the number of cascaded stages. This structure was improved in [2] by reversing the cascading order to increase output conductance and in [3] by using a positive feedback approach. However, this design still provides less output conductance than previous works offering only a small fixed number of ratios [4,5]. This paper presents an SC DC-DC converter that can be reconfigured to have any arbitrary rational conversion ratio: p/q, 0<;p<;q≤2N+1. The key idea of the design, which we refer to as a rational DC-DC converter, is to incorporate negative voltage feedback into the cascaded converter stages using negative-generating converter stages (“voltage negators”); this enables reconfiguring of both the numerator p and denominator q of the conversion ratio. With help from the current supply of the voltage negators, output conductance becomes comparable to conventional few-ratio SC DC-DC designs. Hence, the proposed design achieves a resolution higher than previous binary SC converters while maintaining the conversion efficiency of dedicated few-ratio SC converters. Using only 3 cascaded converter stages and 2 voltage negator stages, the rational converter implemented in 0. 18μm CMOS offers 79 conversion ratios and achieves >90% efficiency when downconverting from 2V to a 1.1-to-1.86V output voltage range.
Occupational Therapy for Upper Limb Post-Stroke Sensory Impairments: A Survey

Purpose: Upper limb post-stroke sensory impairments have an impact on a significant number of stroke survivors. There is limited research in this area and it is unclear how occupational therapists are addressing sensory impairments in clinical practice. This study aimed to investigate the clinical practice patterns of occupational therapists, perceived barriers to providing interventions and information sources used when addressing upper limb post-stroke sensory impairments. Methods: A survey was sent to 500 randomly selected occupational therapists in the United States. Findings: The majority of the 145 respondents reported frequently assessing sensation, and half reported providing interventions for sensory impairments. Interventions primarily focused on providing passive sensory stimulation followed by compensatory strategies. Most therapists provided patient/caregiver education about safety. Therapists cited lack of knowledge and skills, patients' short length of stay and lack of time as barriers to utilizing interventions. Most therapists reported not being up to date with current research and requested continuing education to support practice. Conclusion: This survey established a profile of American occupational therapists' practice with people with upper limb post-stroke sensory impairments. Therapists have a need for information and training in all aspects of the management of upper limb post-stroke sensory impairment. Further research, evaluating the effectiveness of interventions and exploring therapists' clinical decision making when choosing interventions, is also needed.
IL‐1β differently stimulates proliferation and multinucleation of distinct mouse bone marrow osteoclast precursor subsets

Osteoclasts are bone‐resorbing cells and targets for treating bone diseases. Previously, we reported that distinct murine osteoclast precursor subsets, such as early blasts (CD31hi Ly‐6C−), myeloid blasts (CD31+ Ly‐6C+), and monocytes (CD31− Ly‐6Chi), respond differently to the osteoclastogenesis‐inducing cytokines, macrophage colony‐stimulating factor, and receptor activator for nuclear factor κB ligand. It is unknown, however, how these cell types respond to the osteoclast‐stimulating inflammatory cytokine interleukin 1β. This study aims to investigate the effect of interleukin 1β on osteoclastogenesis derived from different mouse bone marrow precursors. Early blasts, myeloid blasts, and monocytes were sorted from mouse bone marrow cells using flow cytometry. Cells were cultured on plastic or on bone slices in the presence of macrophage colony‐stimulating factor and receptor activator for nuclear factor κB ligand, without or with interleukin 1β (0.1–10 ng/ml). We found that interleukin 1β stimulated multinucleation and bone resorption of osteoclasts derived from the 3 precursors at different rates. The most large osteoclasts (>20 nuclei) and highest level of bone resorption (16.3%) was by myeloid blast–derived osteoclasts. Interleukin 1β particularly accelerated proliferation of early blasts and the most small osteoclasts (3–5 nuclei) formed on plastic. Life span varied among osteoclasts derived from different precursors: large osteoclasts (>2400 µm2) formed most rapidly (75 h) from myeloid blasts but had a short life span (30 h). Monocytes needed the longest time (95 h) for the generation of such large osteoclasts, but these cells had a longer life span (50 h). Our results indicate that the different bone marrow osteoclast precursors are differently stimulated by interleukin 1β with respect to proliferation, multinucleation, life span, and bone resorption.
OPTN/SRTR 2016 Annual Data Report: Kidney

Data from 2016 show ongoing positive trends in short‐ and long‐term allograft survival, and a decrease in the number of active listed candi‐ dates for the first time in more than a decade, with a concomitant in‐ crease in deceased donor kidney transplants. Transplant rates that had changed dramatically for some groups after implementation of the new kidney allocation system in 2014 are stabilizing, allowing for evaluation of new steady states and trends. Many challenges remain in adult kid‐ ney transplantation, including stagnant rates of living donor transplant, geographic disparities in access to transplant, racial disparities in living donor transplant, and overall a continuing demand for kidneys that far outpaces the supply. For pediatric recipients, a decline in the proportion of living donor transplants is of concern. In 2016, only 34.2% of pediatric transplants were from living donors, compared with 47.2% in 2005. The number of related donors decreased dramatically over the past decade, and the number of unrelated directed transplants performed in pediatric candidates remained low (50).
DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing

Background The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown. Objective To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family. Methods We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA. Results We identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I. Conclusions To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.
An overview of clinical manifestations and survival of systemic lupus erythematosus patients in Asia

Aim: To provide an overview of the clinical manifestations, survival and causes of mortality of systemic lupus erythematosus (SLE) patients in Asia. Methods: Literature retrieval utilized the following sources: (i) computerized bibliographic database of the National Library of Medicine (MEDLINE 1986–2006) by PubMed; (ii) articles on SLE published in journals of national medical or rheumatology societies; and (iii) abstracts presented in national, regional and international rheumatology and SLE conferences. The available materials were cited to summarize and extrapolate data deemed most representative of each Asian country. Results: The average age at SLE diagnosis ranged from 24–33 years, with a ratio ranging from 8–28 females to one male. Cutaneous and musculoskeletal manifestations were the most frequently observed, ranging from 45–98% and 36–85%, respectively. Renal involvement ranged from 6–100% (overall), or 26–74% (excluding presenting manifestations, and data obtained from a renal centre). Survival rates ranged from 65–98% at 5 years, and 50–84% at 10 years, with a trend for improved survival in more recent reports. Infection and active SLE disease were the predominant causes of mortality, with renal and central nervous system involvement as the main organs involved at time of death. Summary: This overview substantiates the potential vastness of clinical material on SLE in Asia, and reinforces the need for concerted efforts to encourage more research designed to address special issues and develop a more efficient health care delivery system tailored to the Asian lupus patient.
The marketing of nicotine addiction by one oral snuff manufacturer

Massachusetts Tobacco Control Program, Massachusetts Department of Public Health, 150 Tremont Street, Boston, Massachusetts 02111, USA GN Connolly Abstract Oral snuff is a form of smokeless tobacco that has been shown to cause oral cancer, gum disease, and nicotine dependence. Since 1970 use of oral snuff has soared among young males. I believe this in creased use is a direct result of an industry advertising and marketing campaign that encourages young non users to experiment with low nicotine starter products with the intent of gradu ating new users up to higher nicotine brands as dependence progresses. This article reviews internal industry docu ments offered into evidence in a 1986 Oklahoma court case, tobacco and adver tising industry trade literature, and advertising and promotional material that shows how one snuff manufacturer markets nicotine dependence to young people.