Miracle-dz/UniFAR-FTUs huggingface dataset:
Minimax design of adjustable-bandwidth linear-phase FIR filters

This paper considers the design of digital linear-phase finite-length impulse response (FIR) filters that have adjustable bandwidth(s) whereas the phase response is fixed. For this purpose, a structure is employed in which the overall transfer function is a weighted linear combination of fixed subfilters and where the weights are directly determined by the bandwidth(s). Minimax design techniques are introduced which generate globally optimal overall filters in the minimax (Chebyshev) sense over a whole set of filter specifications. The paper also introduces a new structure for bandstop and bandpass filters with individually adjustable upper and lower band edges, and with a substantially lower arithmetic complexity compared to structures that make use of two separate adjustable-bandwidth low-pass and high-pass filters in cascade or in parallel. Design examples are included in the paper.
Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody

An antibody to block viral fusion A small fraction of HIV-1–infected individuals develop broad and potent antibodies that bind the HIV-1 envelope protein (Env). These antibodies recognize a limited set of conserved epitopes on Env, such as Env's host receptor-binding site. Kong et al. now report a neutralizing antibody isolated from an HIV-1–infected individual that binds to the fusion peptide of Env. This is unexpected because viruses often try to mask such key components of their cell entry machinery from antibody attack. Crystal structures of the antibody bound to the fusion peptide and to Env itself define the epitope, provide insight into the specific mechanism of antibody binding, and may inform HIV-1 vaccine design. Science, this issue p. 828 A neutralizing antibody against HIV-1 unexpectedly targets a key component of the virus’ cell entry machinery. The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.
Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity

Cyclin suppresses antitumor immunity Despite the dramatic success of cancer immunotherapy, many types of cancer do not respond. Understanding why could help us to find ways to enhance the overall responsiveness of tumors to immunotherapies. Dorand et al. report that cyclin-dependent kinase 5 (Cdk5), an enzyme that is highly expressed by neurons in many brain cancers, may dampen the ability of T cells to reject tumors. In a mouse model of medulloblastoma, if tumors were Cdk5 deficient, T cells were able to remove them. This heightened antitumor immunity correlated with reduced expression of the inhibitory molecule programmed cell death ligand 1 (PD-L1), a target of current cancer immunotherapies. Science, this issue p. 399 Cyclin-dependent kinase 5 expression by tumors inhibits antitumor immunity in human and mouse medulloblastoma. Cancers often evade immune surveillance by adopting peripheral tissue– tolerance mechanisms, such as the expression of programmed cell death ligand 1 (PD-L1), the inhibition of which results in potent antitumor immunity. Here, we show that cyclin-dependent kinase 5 (Cdk5), a serine-threonine kinase that is highly active in postmitotic neurons and in many cancers, allows medulloblastoma (MB) to evade immune elimination. Interferon-γ (IFN-γ)–induced PD-L1 up-regulation on MB requires Cdk5, and disruption of Cdk5 expression in a mouse model of MB results in potent CD4+ T cell–mediated tumor rejection. Loss of Cdk5 results in persistent expression of the PD-L1 transcriptional repressors, the interferon regulatory factors IRF2 and IRF2BP2, which likely leads to reduced PD-L1 expression on tumors. Our finding highlights a central role for Cdk5 in immune checkpoint regulation by tumor cells.
The fitness landscape of a tRNA gene

Epistasis and mutational fitness landscape A fitness landscape of a gene defines the molecular potential of evolution. This can help us understand the current state of evolution as well as predict unrealized potential. Using deep sequencing to examine mutations in nonessential genes that affect the growth of yeast strains, two studies have generated fitness landscapes and measured the effect of epistatic interactions (see the Perspective by He and Liu). Li et al. generated a library of mutants in a transfer RNA gene, including all single and many double and multiple mutants. The RNA secondary structure was generally predictive of bases under selection. Similarly, Puchta et al. assessed a small nucleolar RNA gene for the fitness effects of individual mutations, which correlated with evolutionary conservation and structural stability. Both studies suggest that epistasis—the combined functional effect—for double substitutions is more often negative than positive. Science, this issue pp. 837 and 840; see also p. 769 Between-site epistasis is pervasive in a transfer RNA gene with patterns explained by the structure of the molecule. Fitness landscapes describe the genotype-fitness relationship and represent major determinants of evolutionary trajectories. However, the vast genotype space, coupled with the difficulty of measuring fitness, has hindered the empirical determination of fitness landscapes. Combining precise gene replacement and next-generation sequencing, we quantified Darwinian fitness under a high-temperature challenge for more than 65,000 yeast strains, each carrying a unique variant of the single-copy tRNACCUArg gene at its native genomic location. Approximately 1% of single point mutations in the gene were beneficial and 42% were deleterious. Almost half of all mutation pairs exhibited statistically significant epistasis, which had a strong negative bias, except when the mutations occurred at Watson-Crick paired sites. Fitness was broadly correlated with the predicted fraction of correctly folded transfer RNA (tRNA) molecules, thereby revealing a biophysical basis of the fitness landscape.
Detection of an oxygen emission line from a high-redshift galaxy in the reionization epoch

Shining brightly in the early universe Galaxies that formed early in the history of the universe were powerful sources of ultraviolet radiation. This radiation ionized the surrounding intergalactic medium during the “epoch of reionization. ” Inoue et al. detected atomic emission lines from a galaxy at high redshift—seen as it was when the universe was only ~5% of its current age (see the Perspective by De Breuck). Data from optical, infrared, and submillimeter observatories determined its gas and dust content and the amount of ultraviolet radiation it emitted. Studying similar galaxies in such a manner will allow astronomers to determine how the first galaxies formed, evolved, and influenced their surroundings. Science, this issue p. 1559; see also p. 1520 A galaxy shining brightly in the early universe emits copious ultraviolet radiation. The physical properties and elemental abundances of the interstellar medium in galaxies during cosmic reionization are important for understanding the role of galaxies in this process. We report the Atacama Large Millimeter/submillimeter Array detection of an oxygen emission line at a wavelength of 88 micrometers from a galaxy at an epoch about 700 million years after the Big Bang. The oxygen abundance of this galaxy is estimated at about one-tenth that of the Sun. The nondetection of far-infrared continuum emission indicates a deficiency of interstellar dust in the galaxy. A carbon emission line at a wavelength of 158 micrometers is also not detected, implying an unusually small amount of neutral gas. These properties might allow ionizing photons to escape into the intergalactic medium.
A 16-Bit Barrel-Shifter Implemented in Data-Driven Dynamic Logic ($D ^3 L$)

Data-driven dynamic logic (D3L) uses local data instead of a global clock to maintain correct precharge and evaluation phases. Eliminating the clock from dynamic gates yields less power consumption and faster gate operation. Two 16-bit barrel shifters are implemented in a 5-V 0.6-mum CMOS technology: one in normal Domino logic and the other in our proposed D3L. Separate power leads are used on the chip to measure power consumption of separate sections. Post-layout simulations show that, depending on input patterns, a D3L shifter consumes 8% to 62% less power and is 29% faster than the Domino circuit. In addition, it provides an additional 9% area advantage over its Domino rival. Experimental measurements confirm post-layout simulation results, and prove the feasibility of the proposed logic
UvA-DARE (Digital Academic Repository) Orbital-exchange and fractional quantum number excitations in an f-electron metal, Yb 2 Pt 2 Pb

Exotic quantum states and fractionalized magnetic excitations, such as spinons in one-dimensional chains, are generally expected to occur in 3d transition metal systems with spin 1/2. Our neutron-scattering experiments on the 4f-electron metal Yb 2 Pt 2 Pb overturn this conventional wisdom.We observe broad magnetic continuum dispersing in only one direction, which indicates that the underlying elementary excitations are spinons carrying fractional spin-1/2. These spinons are the emergent quantum dynamics of the anisotropic, orbital-dominated Yb moments. Owing to their unusual origin, only longitudinal spin fluctuations are measurable, whereas the transverse excitations such as spin waves are virtually invisible to magnetic neutron scattering. The proliferation of these orbital spinons strips the electrons of their orbital identity, resulting in charge-orbital separation.
Treatment Approaches to Major Depressive Disorder Relapse

Objective: Although continuing antidepressant treatment after patients have responded to medication has been shown to greatly reduce the risk of relapse, this risk is not eliminated. A number of theories have been proposed to account for this apparent loss of efficacy. A common initial approach to managing relapse is to increase the dose of antidepressant. We prospectively evaluated the likelihood of response to increasing the fluoxetine doses in patients relapsing during a long-term efficacy study of two fluoxetine dosing regimens. Method: Patients meeting the DSM-IV criteria for major depressive disorder with modified HAMD17 scores ≧18 and CGI-severity scores ≧4 were treated for 13 weeks with open-label 20 mg/day fluoxetine in a multicenter US study. Responders (n = 501) were randomized to 20 mg fluoxetine daily, placebo, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. If the patients relapsed during the continuation phase, they were offered a 25-week optional rescue treatment phase during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/day reinitiated, (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. The results of the rescue phase for the latter two groups who relapsed while on continuation treatment with fluoxetine are reported. Response was defined as a 50% reduction in the modified HAMD17 score since time of relapse and a CGI-severity score ≤2. Additional efficacy analyses included HAMD and CGI-severity changes from baseline to endpoint. Safety measures included assessment of treatment-emergent adverse events, vital signs, and laboratory measures. Results: Overall, patients relapsing during the continuation treatment responded to an increased dose (57% of the 40-mg-daily group and 72% of the enteric-coated 90-mg-twice-weekly group). Mean modified HAMD17 scores decreased from a mean of approximately 20 to below 8 and were maintained for up to 6 months in the responders. Thirty-five percent of patients either did not respond or initially responded but again relapsed after augmentation of medication. Conclusions: The patients relapsing after initially responding to fluoxetine can benefit from an increase in fluoxetine dose. These results also generally support increasing dose as a first-line treatment strategy for a patient who has relapsed while taking a previously effective dose of an antidepressant. Increasing enteric-coated fluoxetine 90 mg once weekly to twice weekly appeared to be as well-tolerated and effective in restoring response as increasing a daily fluoxetine dose from 20 to 40 mg.
SCS macrophages suppress melanoma by restricting tumor-derived vesicle–B cell interactions

Macrophages block tumors' spread Tumors constantly communicate with their surrounding tissue and the immune system. One way tumors likely do this is by secreting extracellular vesicles (tEVs), which can carry bits of the tumor to distant sites in the body. Pucci et al. tracked tEVs in tumor-bearing mice and people and studied how they affect cancer progression. They found that tEVs disseminate through lymph to nearby lymph nodes, where a specialized population of macrophages largely block any further travel. This barrier breaks down, however, as cancer progresses and also in the face of certain therapies. The tEVs can then penetrate lymph nodes, where they interact with B cells that promote further tumor growth. Science, this issue p. 242 Lymph node macrophages provide a physical barrier against tumor spread. Tumor-derived extracellular vesicles (tEVs) are important signals in tumor–host cell communication, yet it remains unclear how endogenously produced tEVs affect the host in different areas of the body. We combined imaging and genetic analysis to track melanoma-derived vesicles at organismal, cellular, and molecular scales to show that endogenous tEVs efficiently disseminate via lymphatics and preferentially bind subcapsular sinus (SCS) CD169+ macrophages in tumor-draining lymph nodes (tdLNs) in mice and humans. The CD169+ macrophage layer physically blocks tEV dissemination but is undermined during tumor progression and by therapeutic agents. A disrupted SCS macrophage barrier enables tEVs to enter the lymph node cortex, interact with B cells, and foster tumor-promoting humoral immunity. Thus, CD169+ macrophages may act as tumor suppressors by containing tEV spread and ensuing cancer-enhancing immunity.
Conversion of human fibroblasts into functional cardiomyocytes by small molecules

Making cardiac cells from fibroblasts Reprogramming noncardiac cells into functional cardiomyocytes without any genetic manipulation could open up new avenues for cardiac regenerative therapies. Cao et al. identified a combination of nine small molecules that could epigenetically activate human fibroblasts, efficiently reprogramming them into chemically induced cardiomyocytes (ciCMs). The ciCMs contracted uniformly and resembled human cardiomyocytes. This method may be adapted for reprogramming multiple cell types and have important implications in regenerative medicine. Science, this issue p. 1216 Heart-like cells can be generated from human skin cells by using small molecules and without genetic manipulation. Reprogramming somatic fibroblasts into alternative lineages would provide a promising source of cells for regenerative therapy. However, transdifferentiating human cells into specific homogeneous, functional cell types is challenging. Here we show that cardiomyocyte-like cells can be generated by treating human fibroblasts with a combination of nine compounds that we term 9C. The chemically induced cardiomyocyte-like cells uniformly contracted and resembled human cardiomyocytes in their transcriptome, epigenetic, and electrophysiological properties. 9C treatment of human fibroblasts resulted in a more open-chromatin conformation at key heart developmental genes, enabling their promoters and enhancers to bind effectors of major cardiogenic signals. When transplanted into infarcted mouse hearts, 9C-treated fibroblasts were efficiently converted to chemically induced cardiomyocyte-like cells. This pharmacological approach to lineage-specific reprogramming may have many important therapeutic implications after further optimization to generate mature cardiac cells.
Analysis of a multi-centric pooled healthcare associated infection data from India: New insights

Aim: The aim of this study was to analyze the multi-center data of healthcare associated infections (HAIs) to assess the infection control (IC) scenario in India in context with Center for Disease Control (CDC)/National Healthcare Safety Network (NHSN) and International Nosocomial Infection Control Consortium (INICC) database. Materials and Methods: Four National Accreditation Board for Hospitals accredited hospitals contributed their raw data on HAIs-number of days and number of infections in all intensive care patients were obtained as per the CDC-NHSN definitions and formulae. Three major device related infections were considered for analysis based on the prevalence of HAIs and discussions with subject experts. All nodal champions from each hospital were trained and common data collection sheet for surveillance in accordance to CDC-NHSN was formed. The pooled means for HAI rates and average of the pooled means for all were calculated using data from them and compared with CDC/NHSN and INICC percentiles. Results: The Indian pooled mean HAI rates for all infections were above CDC/NHSN percentile threshold but below INICC percentile. Ventilator associated pneumonia was considered as a matter of prime concern, crossing P90 line of CDC/NHSN threshold. However, no HAI rate was in the limit of P25. Conclusion: Indian HAI rates were higher when mapped with CDC threshold. This suggests the requirement for more standardized and evidence based protocols to tackle the HAIs with an aim to achieve the benchmark within CDC/NHSN thresholds. However, the 4 hospitals have better HAI rates as compared to pooled INICC database.
A Versatile Time-Domain Approach to Simulate Oscillators in RF Circuits

This paper presents a versatile simulation technique for the time-domain analysis of RF oscillators. The method blends the superior accuracy and robustness of implicit Runge-Kutta integration formulas with the high efficiency of a particular envelope-following technique. The method can be applied to study both transient and steady-state responses of autonomous and nonautonomous circuits and can also be applied to the case of harsh nonlinear oscillator topologies.
Evaluation of the Degree of Agreement in Identifying Lip Prints and Palatal Rugae by three Independent Observers and Valuation of there Dependability in Sex Determination

Background : Establishing a person's identity is a very important process in civil and criminal cases. Dental, fingerprint and DNA comparisons are probably the most common techniques allowing fast and secure identification processes. However, in certain circumstances related to the scene of the crime or due to lack of experienced personnel, these techniques might be unavailable, so there is still an increasing need for reliable alternative methods of establishing identity. Objective : The objective of the study was to check for any peculiar lip patterns and rugae patterns in relation to the sex of the individual and to analyze the degree of agreement between three observers. Materials and Method: This study was conducted on 378 subjects, which included 189 males and 189 females, in the age group of 18-30 years. Lip prints and rugae pattern were analysed by three independent observers. Results : Lip print of branched type was most commonly seen in females and cross-section in males. Wavy pattern was most common in males and females in palatal rugae. Conclusion: This study shows that lip prints and palatal rugae are unique to an individual and behold the potential for recognition of the sex of an individual.
High-Performance Special Function Unit for Programmable 3-D Graphics Processors

An high-speed special function unit (SFU) is presented in this paper. The system supports the single-precision IEEE-754 floating-point standard and implements faithfully rounded reciprocal, square root, reciprocal square root, logarithm, and exponential functions. The functions are approximated by using a novel constrained piecewise quadratic interpolation technique. In this way, the lookup table size is reduced by 40% with respect to previously proposed techniques, without any loss in accuracy. Error analysis and sizing methodology are presented in the paper. The SFU has been implemented in a 0.18-mum CMOS technology. The circuit is able to operate up to 420-MHz clock frequency, with a power dissipation of 160 mW at 420 MHz. The system can be employed in programmable graphics accelerators and in other applications where high-performance function evaluation is needed.
Peering through Jupiter’s clouds with radio spectral imaging

A radio view into Jupiter's atmosphere Jupiter's atmosphere is a complex system of belts, layers, storms, and cloud systems. de Pater et al. used Earth-bound radio observations to peer beneath its surface. Previous radio studies have been limited to average properties at each latitude, but the new observations allow a full two-dimensional view. This can be related to features (such as storms) seen in visible or infrared images. The results aid our understanding of gas giant atmospheres and will provide important context for the Juno spacecraft that arrives at Jupiter in July 2016. Science, this issue p. 1198 Radio observations probe beneath the clouds of Jupiter’s atmosphere. Radio wavelengths can probe altitudes in Jupiter’s atmosphere below its visible cloud layers. We used the Very Large Array to map this unexplored region down to ~8 bar, ~100 kilometers below the visible clouds. Our maps reveal a dynamically active planet at pressures less than 2 to 3 bar. A radio-hot belt exists, consisting of relatively transparent regions (a low ammonia concentration, NH3 being the dominant source of opacity) probing depths to over ~8 bar; these regions probably coincide with 5-micrometer hot spots. Just to the south we distinguish an equatorial wave, bringing up ammonia gas from Jupiter’s deep atmosphere. This wave has been theorized to produce the 5-micrometer hot spots; we observed the predicted radio counterpart of such hot spots.